1
UI - 16
AU - Barrionuevo M
AU - Aguirre N
AU - Del Rio JD
AU - Lasheras B
AD - Department of
Pharmacology, University of Navarra, Pamplona, Spain
TI - Serotonergic
deficits and impaired passive-avoidance learning in rats by MDEA: a comparison
with MDMA
AB - The
serotonergic deficits induced by 3,4-methylenedioxyethamphetamine (MDEA,
"eve"), were examined and compared with 3,4 methylenedioxymethamphetamine
(MDMA, "ecstasy"). A single dose of MDEA (10, 20, or 40 mg/kg IP)
induced a dose-related hyperthermia, but only the highest dose significantly
reduced 5-HT content and 5-HT transporter density in the frontal cortex and in
the hippocampus 7 days later. Long-term serotonergic deficits were much more
marked when MDEA was given repeatedly (40 mg/kg IP., b.i.d., for 4 consecutive
days). Single or repeated administration of MDEA induced no change on 5-HT1A
receptor density in the frontal cortex, brain stem, or hippocampus, although 3
h after both treatments plasma corticosterone levels were significantly
increased. MDEA (5-20 mg/kg, IP) produced significant retention deficits in a
passive-avoidance learning task. Conversely, 7 days after the repeated administration
of MDEA (40 mg/kg b.i.d., for 4 consecutive days) no effect on
passive-avoidance performance was observed unless rats were treated again with
another dose of MDEA (20 mg/kg IP) 30 min before the training trial. The 5-HT1A
receptor antagonist, WAY 100635, prevented the impairment in retention
performance induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH- DPAT), but
not by MDEA or MDMA, indicating that the effect of these amphetamine derivates
was not mediated by 5-HT1A receptor activation. The results suggest the risk of
serotonergic dysfunction associated with MDEA abuse in humans
MH - Animal
MH - Avoidance
Learning
MH - drug effects
MH - Carrier
Proteins
MH - metabolism
MH - Designer Drugs
MH - pharmacology
MH - Frontal Lobe
MH - Hippocampus
MH - Male
MH - Membrane
Glycoproteins
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Paroxetine
MH - Rats
MH - Rats,Wistar
MH -
Receptors,Serotonin
MH - Serotonin
MH - Serotonin
Agents
MH - Serotonin
Uptake Inhibitors
MH - Support,Non-U.S.Gov't
MH -
3,4-Methylenedioxyamphetamine
MH - analogs &
derivatives
RP - NOT IN FILE
NT - UI - 20135529LA
- EngRN - 0 (serotonin transporter)RN - 0 (Carrier Proteins)RN - 0 (Designer
Drugs)RN - 0 (Membrane Glycoproteins)RN - 0 (Receptors, Serotonin)RN - 0
(Serotonin Agents)RN - 0 (Serotonin Uptake Inhibitors)RN - 112692-38-3
(serotonin 1A receptor)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 61869-08-7 (Paroxetine)RN
- 82801-81-8 (3,4-methylenedioxyethamphetamine)PT - JOURNAL ARTICLEDA -
20000314IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 200005
UR - PM:0010672974
SO - Pharmacol
Biochem Behav 2000 Feb ;65(2):233-240
2
UI - 2
AU - Boot BP
AU - McGregor IS
AU - Hall W
AD - Faculty of
Medicine, University of Sydney, NSW, Australia
TI - MDMA (Ecstasy)
neurotoxicity: assessing and communicating the risks [In Process Citation]
RP - NOT IN FILE
NT - UI - 20290449LA
- EngDA - 20000530IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SRO -
O:099
UR - PM:0010832852
SO - Lancet 2000 May
20 ;355(9217):1818-1821
3
UI - 13
AU - Chang L
AU - Grob CS
AU - Ernst T
AU - Itti L
AU - Mishkin FS
AU - Jose-Melchor R
AU - Poland RE
AD - Department of
Neurology, UCLA School of Medicine, Harbor-UCLA Medical Center, 1000 W. Carson
Street, B-4, Torrance, CA 90509, USA. linda_chang@humc.edu
TI - Effect of
ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a
co-registered SPECT and MRI study
AB -
3,4-methylenedioxymethamphetamine (MDMA), an illicit recreational drug, damages
serotonergic nerve endings. Since the cerebrovasculature is regulated partly by
the serotonergic system, MDMA may affect cerebral blood flow (CBF) in humans.
We evaluated 21 abstinent recreational MDMA users and 21 age- and
gender-matched healthy subjects with brain SPECT and MRI. Ten of the MDMA
subjects also had repeat SPECT and MRI after receiving two doses of MDMA.
Abstinent MDMA users showed no significantly different global or regional CBF
(rCBF) compared to the control subjects. However, within 3 weeks after MDMA
administration, rCBF remained decreased in the visual cortex, the caudate, the
superior parietal and dorsolateral frontal regions compared to baseline rCBF.
The decreased rCBF tended to be more pronounced in subjects who received the
higher dosage of MDMA. Two subjects who were scanned at 2- 3 months after MDMA
administration showed increased rather than decreased rCBF. Low-dose
recreational MDMA use does not cause detectable persistent rCBF changes in
humans. The lack of long-term rCBF changes may be due to a non-significant
effect of serotonergic deficits on rCBF, or regeneration of serotonergic nerve
terminals. The subacute decrease in rCBF after MDMA administration may be due
to the direct effect of MDMA on the serotonergic system or the indirect effects
of its metabolites on the dopaminergic system; the preliminary data suggest
these effects may be transient
MH - Adult
MH - Brain
MH - drug effects
MH - pathology
MH - radionuclide
imaging
MH - Case-Control
Studies
MH - Cerebrovascular
Circulation
MH - Dose-Response
Relationship,Drug
MH - Female
MH - Human
MH - Magnetic
Resonance Imaging
MH - Male
MH - Middle Age
MH - N-Methyl-3,4-methylenedioxyamphetamine
MH - administration
& dosage
MH - adverse effects
MH -
Radiopharmaceuticals
MH - diagnostic use
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
MH - Technetium Tc
99m Exametazime
MH - Time Factors
MH -
Tomography,Emission-Computed,Single-Photon
RP - NOT IN FILE
NT - UI - 20175743LA
- EngRN - 0 (Radiopharmaceuticals)RN - 0 (Serotonin Agents)RN - 0 (Technetium
Tc 99m Exametazime)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT -
JOURNAL ARTICLEID - DA00280/DA/NIDAID - MO1 RR00425/RR/NCRRID -
MH00534/MH/NIMHDA - 20000509IS - 0165-1781SB - MCY - IRELANDJC - QC4AA -
AuthorEM - 200007
UR - PM:0010708923
SO - Psychiatry Res
2000 Feb 28 ;98(1):15-28
4
UI - 17
AU - de la TR
AU - Farre M
AU - Ortuno J
AU - Mas M
AU - Brenneisen R
AU - Roset PN
AU - Segura J
AU - Cami J
AD - Pharmacology
Research Unit, Institut Municipal d'Investigacio Medica (IMIM), Universitat
Pompeu Fabra and Universitat Autonoma de Barcelona, Spain. rtorre@imim.es
TI - Non-linear
pharmacokinetics of MDMA ('ecstasy') in humans
AB - AIMS:
3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a
synthetic compound increasingly popular as a recreational drug. Little is known
about its pharmacology, including its metabolism and pharmacokinetics, in
humans in controlled settings. A clinical trial was designed for the evaluation
of MDMA pharmacological effects and pharmacokinetics in healthy volunteers.
METHODS: A total of 14 subjects were included. In the pilot phase six received
MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight
received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6
activity and were classified as extensive metabolizers for substrates, such as
MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine
samples were collected throughout the study for the evaluation of MDMA
pharmacokinetics. Body fluids were analysed for the determination of MDMA and
its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-
hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy- amphetamine
(HMA). RESULTS: As the dose of MDMA administered was increased, volunteers
showed rises in MDMA concentrations that did not follow the same
proportionality which could be indicative of nonlinearity. In the full range of
doses tested the constant recovery of HMMA in the urine combined with the
increasing MDMA recovery seems to point towards a saturation or an inhibition
of MDMA metabolism (the demethylenation step). These observations are further
supported by the fact that urinary clearance was rather constant while nonrenal
clearance was dose dependent. CONCLUSIONS: It has previously been postulated
that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10%
of the Caucasian people) were at risk of developing acute toxicity at moderate
doses of MDMA because the drug would accumulate in the body instead of being
metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in
a window of doses compatible with its recreational use) is a more general
phenomenon as it concerns the whole population independent of their CYP2D6
genotype. It implies that relatively small increases in the dose of MDMA
ingested are translated to disproportionate rises in MDMA plasma concentrations
and hence subjects are more prone to develop acute toxicity
MH - Adult
MH - Area Under
Curve
MH - Blood Pressure
MH - drug effects
MH - Cross-Over
Studies
MH -
Deoxyepinephrine
MH - analogs &
derivatives
MH - urine
MH - Diastole
MH - Dose-Response
Relationship,Drug
MH - Double-Blind
Method
MH - Hallucinogens
MH - blood
MH -
pharmacokinetics
MH - Human
MH - Hydrogen-Ion
Concentration
MH - Male
MH - Metabolic
Clearance Rate
MH - Methamphetamine
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Pilot Projects
MH -
Support,Non-U.S.Gov't
MH - Time Factors
MH -
3,4-Methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 20137822LA
- EngRN - 0 (Hallucinogens)RN - 117652-28-5
(4-hydroxy-3-methoxymethamphetamine)RN - 15398-87-5 (alpha-methylepinine)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4 (3,4-Methylenedioxyamphetamine)RN
- 501-15-5 (Deoxyepinephrine)RN - 537-46-2 (Methamphetamine)PT - CLINICAL
TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED CONTROLLED TRIALDA - 20000302IS -
0306-5251SB - MCY - ENGLANDJC - AU9AA - AuthorEM - 200005
UR - PM:0010671903
SO - Br J Clin
Pharmacol 2000 Feb ;49(2):104-109
5
UI - 6
AU -
Erdtmann-Vourliotis M
AU - Mayer P
AU - Riechert U
AU - Hollt V
AD - Institute for
Pharmacology and Toxicology, Otto-von-Guericke Universitat, Leipziger Str. 44,
39120, Magdeburg, Germany
TI - Prior
experience of morphine application alters the c-fos response to MDMA
('ecstasy') and cocaine in the rat striatum [In Process Citation]
AB - Repeated
morphine application usually leads to the development of tolerance but under
certain circumstances sensitization may arise simultaneously. This phenomenon
becomes obvious in behavioral tests as increasing locomotor activity and
increasing drug self-administration during a course of chronic morphine
application. It was suggested recently that sensitization could contribute to
addiction. The molecular mechanisms of sensitization may include the long
lasting increase in neuronal responsiveness to morphine which was observed in
defined brain areas after repeated morphine injections. In this work, we
studied whether morphine-sensitized Wistar rats also display an enhanced
neuronal activity in response to other drugs of abuse (so called
co-sensitization). The substances to be tested were injected as single doses 4
weeks after completion of a 10-day morphine pretreatment. MDMA (3, 4-methylenedioxymethamphetamine,
6 mg/kg) as a single test dose yielded a c-fos response in a wide range of
brain areas. In the caudate putamen, the expression pattern of c-fos was
clearly altered if the rats had received repeated morphine application
previously. In this case, the MDMA-induced c-fos expression was markedly
confined to the centromedial, mesolimbic aspect of the striatum whereas it had
a diffuse appearance in rats not exposed to the opiate earlier. Cocaine
application (50 mg/kg) elicited an intense c- fos expression in the medial
striatum if the animals were morphine- pretreated; it was virtually absent in
drug-naive rats after the same cocaine dose. Ten mg/kg cocaine had a similar
but weaker effect. No difference in the c-fos expression pattern between morphine
and saline pretreated animals was observed in the case of a THC (Delta(9)-
tetrahydrocannabinol, 25 mg/kg) or an LSD (lysergic acid diethylamide, 1 mg/kg)
test application. These findings imply that morphine sensitizes the brain
towards other addicting drugs. In consequence, morphine sensitization obviously
does not solely reflect alterations in &mgr;-opioid receptor signaling.
Rather, it seems to reflect further rearrangements within the mesolimbic system
RP - NOT IN FILE
NT - UI - 20276033LA
- EngDA - 20000617IS - 0169-328XSB - MCY - NETHERLANDSJC - MBRAA - AUTHORRO -
O:099
UR - PM:0010814832
SO - Brain Res Mol
Brain Res 2000 Apr 14 ;77(1):55-64
6
UI - 9
AU - Fischer HS
AU - Zernig G
AU - Schatz DS
AU - Humpel C
AU - Saria A
AD - Division of
Neurochemistry, Department of Psychiatry, Anichstrasse 35, A-6020 Innsbruck,
Austria
TI - MDMA
('ecstasy') enhances basal acetylcholine release in brain slices of the rat
striatum [In Process Citation]
AB - The
pharmacological basis of acute (+/-)-MDMA (3, 4- methylenedioxymethamphetamine)
intoxication still awaits full characterization. According to present
knowledge, MDMA enhances the release of serotonin and dopamine in striatal
slices and interacts with different types of receptors such as 5-HT2
(5-hydroxytryptamine or serotonin), M1 and M2 muscarinic acetylcholine (ACh),
and histamine H1 receptors. Currently, no information is available about the
influence of (+/-)-MDMA on striatal cholinergic neurotransmission. In the
present study, we used the in vitro perfusion technique to investigate the
effect of (+/-)-MDMA on ACh release in rat striatal slices. Perfusions with
(+/-)-MDMA (10-300 &mgr;M) resulted in a dose-dependent increase of
spontaneous ACh release (EC50 approximately 30 &mgr;M). The effect was
reversible and Ca++- and tetrodotoxin-sensitive. To determine the neurochemical
pathways underlying this response, we perfused with (+/-)- MDMA in the presence
of various inhibitors of neurotransmitter receptors. Blockade of glutamate or
muscarinic ACh receptors as well as 5-HT1, 5-HT2, 5-HT3C or dopamine D2
receptors did not modulate (+/-)- MDMA-induced ACh release. However, the
presence of histamine H1 receptor antagonists in the perfusion medium abolished
(+/-)-MDMA- induced ACh release. The present data clearly demonstrate that
(+/-)- MDMA enhances the activity of striatal cholinergic neurons and suggest
an involvement of histamine H1 receptors. The effect is not mediated by
glutamate and does not involve the activation of receptors of dopamine D2,
5-HT1, 5-HT2, 5-HT3C or muscarinic ACh. Considering the relatively high
affinity of (+/-)-MDMA for the H1 histamine receptor (Ki 6 &mgr;M), a
direct activation of this type of receptor might represent a plausible
mechanism for (+/-)-MDMA-induced ACh release
RP - NOT IN FILE
NT - UI - 20225557LA
- EngDA - 20000511IS - 0953-816XSB - MCY - FRANCEJC - BYGAA - AUTHORRO - O:099
UR - PM:0010762366
SO - Eur J Neurosci
2000 Apr ;12(4):1385-1390
7
UI - 23
AU - Horan B
AU - Gardner EL
AU - Ashby CR
AD - PHS Department,
College of Pharmacy and Allied Health Professions, St. John's University,
Jamaica, New York 11439, USA
TI - Enhancement of
conditioned place preference response to cocaine in rats following subchronic
administration of 3, 4- methylenedioxymethamphetamine (MDMA)
AB - In this study,
we measured conditioned place preference (CPP) responses to cocaine following
subchronic administration of the recreationally abused drug
(+/-)-3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in male
Sprague-Dawley rats. Animals were given either vehicle (1 ml/kg of distilled
water, s.c.) or MDMA (20 mg/kg, s.c.) twice a day for 4 consecutive days. Two
weeks later, CPP responses to cocaine (5, 10, or 20 mg/kg, i.p.) were measured.
The MDMA-treated animals showed a significantly greater CPP response to cocaine
than the vehicle-treated animals. Since conditioned place preference is
believed to be a measure of appetitive behavior, these results suggest that
MDMA abuse could lead to an increased vulnerability to the rewarding actions of
cocaine and, hence, to increased vulnerability to cocaine addiction and
dependence. Copyright 2000 Wiley-Liss, Inc
MH - Animal
MH - Appetite
MH - drug effects
MH - physiology
MH - Choice Behavior
MH - Cocaine
MH - pharmacology
MH -
Conditioning,Operant
MH - Dose-Response
Relationship,Drug
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Reward
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 20079332LA
- EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-36-2
(Cocaine)PT - JOURNAL ARTICLEID - R29MH55155/MH/NIMHDA - 20000217IS -
0887-4476SB - MCY - UNITED STATESJC - VFLAA - AuthorEM - 200004
UR - PM:0010611642
SO - Synapse 2000
Feb ;35(2):160-162
8
UI - 5
AU - Iravani MM
AU - Asari D
AU - Patel J
AU - Wieczorek WJ
AU - Kruk ZL
AD - Department of
Pharmacology, Queen Mary & Westfield College, University of London, UK.
m.iravani@kcl.ac.uk
TI - Direct effects
of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release
and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars
reticulata, and the dorsal raphe nucleus slices
AB - We examined the
effects of pressure ejected 3, 4- methylenedioxymethamphetamine (MDMA) from a
micropipette on direct chemically stimulated release, and on electrically
stimulated serotonin (5-HT) or dopamine (DA) release in the caudate putamen
(CPu), nucleus accumbens (NAc), substantia nigra pars reticulata (SNr), and the
dorsal raphe nucleus (DRN) brain slices of rat, using fast cyclic voltammetry
(FCV). MDMA is electroactive, oxidising at +1100 mV. When the anodic input
waveform was reduced from +1.4 to +1.0 volt, MDMA was not electroactive. Using
this waveform, pressure ejection of MDMA did not release 5-HT or DA in brain
slices prepared from any of the nuclei studied. MDMA significantly potentiated
electrically stimulated 5-HT release in the SNr and DA release in CPu. In the
DRN or in the NAc, MDMA was without effect on peak electrically stimulated 5-HT
or DA release. The rates of neurotransmitter uptake, expressed as t(1/2), were
in all cases significantly decreased after MDMA. The results indicate that
MDMA, unlike (+)amphetamine, is not as a releaser of DA or 5-HT, it is a potent
inhibitor of both DA and 5-HT uptake. Copyright 2000 Wiley-Liss, Inc
MH - Amphetamine
MH - pharmacology
MH - Animal
MH - Brain
MH - drug effects
MH - metabolism
MH - Caudate Nucleus
MH - Dopamine
MH - Electric
Stimulation
MH -
Electrochemistry
MH - In Vitro
MH - Injections,Jet
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nucleus
Accumbens
MH - Raphe Nuclei
MH - Rats
MH - Rats,Wistar
MH - Serotonin
MH - Substantia
Nigra
RP - NOT IN FILE
NT - UI - 20280163LA
- EngRN - 300-62-9 (Amphetamine)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6
(Dopamine)PT - JOURNAL ARTICLEDA - 20000606IS - 0887-4476SB - MCY - UNITED
STATESJC - VFLAA - AuthorEM - 200008
UR - PM:0010819905
SO - Synapse 2000
Jun 15 ;36(4):275-285
9
UI - 19
AU - Jurado C
AU - Gimenez MP
AU - Soriano T
AU - Menendez M
AU - Repetto M
AD - Instituto
Nacional de Toxicologia, Sevilla, Spain. quim@sev.inaltox.es
TI - Rapid analysis
of amphetamine, methamphetamine, MDA, and MDMA in urine using solid-phase
microextraction, direct on-fiber derivatization, and analysis by GC-MS
AB - A rapid,
sensitive, and solvent-free procedure for the simultaneous determination of
amphetamine, methamphetamine, 3,4- methylenedioxyamphetamine (MDA), and
3,4-methylenedioxymethamphetamine (MDMA) in urine was developed using
solid-phase microextraction (SPME) and gas chromatography-mass spectrometry
(GC-MS) in the selected ion monitoring mode. A headspace vial containing the
urine sample, NaOH, NaCl, and amphetamine-d3 as the internal standard was
heated at 100 degrees C for 20 min. A polydimethylsiloxane fiber was maintained
in the vial headspace for 10 min in order to adsorb the amphetaminic compounds,
which were subsequently derivatized by exposing the fiber to trifluoroacetic
anhydride for 20 min in the headspace of another vial maintained at 60 degrees
C for 20 min. The trifluoroacetyl derivatives were desorbed in the GC injection
port for 5 min. Several parameters were considered during the method
optimization process. These included a comparison of SPME with or without
headspace, the required derivatization procedure, and the influence of
temperature on the headspace extraction and derivatization methods. The
optimized method was validated for the four compounds tested. Calibration
curves showed linearity in the range 50-1000 ng/mL (r = 0.9946-0.9999).
Recovery data were 71.89-103.24%. The quantitation limits were 10 ng/mL for
amphetamine and methamphetamine and 20 ng/mL for MDA and MDMA. All of these
data recommend the applicability of the method for use in the analytical
routine of a forensic laboratory
MH - Amphetamine
MH - urine
MH - Comparative
Study
MH -
Dimethylpolysiloxanes
MH - chemistry
MH - Human
MH - Mass
Fragmentography
MH - Methamphetamine
MH - Microchemistry
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Reproducibility
of Results
MH - Sensitivity and
Specificity
MH - Substance Abuse
Detection
MH - methods
MH -
Sympathomimetics
MH - Temperature
MH - Time Factors
MH -
3,4-Methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 20118724LA
- EngRN - 0 (Dimethylpolysiloxanes)RN - 0 (Sympathomimetics)RN - 300-62-9
(Amphetamine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 537-46-2 (Methamphetamine)PT -
JOURNAL ARTICLEDA - 20000309IS - 0146-4760SB - MCY - UNITED STATESJC - K4RAA -
AuthorEM - 200005
UR - PM:0010654563
SO - J Anal Toxicol
2000 Jan ;24(1):11-16
10
UI - 10
AU - Liechti ME
AU - Baumann C
AU - Gamma A
AU - Vollenweider FX
AD - Psychiatric
University Hospital Zurich. Research Department, P.O. Box 68, CH-8029, Zurich,
Switzerland. mliechti@bli.unizh.ch
TI - Acute
psychological effects of 3,4-methylenedioxymethamphetamine (MDMA,
"Ecstasy") are attenuated by the serotonin uptake inhibitor
citalopram
AB -
3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational
drug that has been shown to release serotonin (5-HT) and dopamine (DA) in
animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake
inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT
uptake site. It is unknown whether this mechanism is also responsible for the
psychological effects of MDMA in humans. We investigated the effect of
citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5
mg/kg po) in a double-blind placebo- controlled psychometric study in 16
healthy human volunteers. MDMA produced an emotional state with heightened
mood, increased self- confidence and extroversion, moderate derealization, and
an intensification of sensory perception. Most of these effects were markedly
reduced by citalopram. This finding suggests that the psychological effects of
MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release
through the carrier, as expected from animal studies
MH - Adult
MH -
Amphetamine-Related Disorders
MH - drug therapy
MH - physiopathology
MH - psychology
MH - Brain
MH - drug effects
MH - Citalopram
MH - administration
& dosage
MH - Double-Blind
Method
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Neuropsychological Tests
MH - Nootropic
Agents
MH - Serotonin
Uptake Inhibitors
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 20197909LA
- EngRN - 0 (Hallucinogens)RN - 0 (Nootropic Agents)RN - 0 (Serotonin Uptake
Inhibitors)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
59729-33-8 (Citalopram)PT - CLINICAL TRIALPT - CONTROLLED CLINICAL TRIALPT -
JOURNAL ARTICLEDA - 20000509IS - 0893-133XSB - MCY - UNITED STATESJC - ADQAA -
AuthorEM - 200007
UR - PM:0010731626
SO -
Neuropsychopharmacology 2000 May ;22(5):513-521
11
UI - 1
AU - Maldonado E
AU - Navarro JF
AD - Area de
Psicobiologia, Facultad de Psicologia, Universidad de Malaga, Spain
TI - Effects of
3,4-methylenedioxy-methamphetamine (MDMA) on anxiety in mice tested in the
light-dark box [In Process Citation]
AB - 1. The effects
of acute administration of 3,4- methylenedioxymethamphetamine (MDMA;
"ecstasy") on anxiety tested in the light/dark box were examined in
albino male mice of the OF.1 strain. 2. Animals were evaluated in the
light/dark test 30 min after injection of MDMA (1, 8, and 15 mg/kg, i.p) or
saline. The following parameters were recorded (for 5 min); (a) number of
exploratory rearings in the light and dark sections; (b) number of transitions
between the lit and dark areas; (c) time spent in the light and dark areas; (d)
latency of the initial movement from the light to the dark area, and (e)
locomotor activity in light area. 3. MDMA (8 and 15 mg/kg) produced a
significant reduction in exploratory activity (rearings and transitions),
without decreasing motility, in comparison with saline-treated mice. However,
time spent in lit/dark compartments was not significantly affected by the drug,
which could be a consequence of the anti-exploratory properties of MDMA. 4.
Overall, the behavioral profile found in the light/dark test indicates an anxiogenic-
like activity of MDMA in mice. It is suggested, however, that animal models of
anxiety which emphasize a social interaction could be more sensitive to the
effects of this substance
RP - NOT IN FILE
NT - UI - 20294482LA
- EngDA - 20000601IS - 0278-5846SB - MCY - ENGLANDJC - Q45AA - AUTHORRO - O:099
UR - PM:0010836493
SO - Prog
Neuropsychopharmacol Biol Psychiatry 2000 Apr ;24(3):463-472
12
UI - 11
AU - McGuire P
AD - Section of
Neuroimaging, Institute of Psychiatry and GKT School of Medicine, London, UK.
p.mcguire@iop.kcl.ac.uk
TI - Long term
psychiatric and cognitive effects of MDMA use
AB - Clinical case
reports suggest that regular MDMA use can be associated with chronic
psychiatric symptoms which persist after the cessation of drug use. Neuropsychological
comparisons of regular MDMA users and controls also suggest that MDMA use may
lead to memory deficits, with other cognitive processes relatively unaffected.
This paper reviews these studies and discusses a number of methodological
issues that impact on the interpretation of the findings. Methods for examining
the biological effects of MDMA use in man are also outlined. Future research
should clarify whether MDMA use has long term psychological effects, and if
these are related to changes in central serotonergic function
MH - Chronic Disease
MH - Cognition
Disorders
MH - chemically
induced
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Memory
Disorders
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neuropsychology
MH - Psychopathology
MH - Recall
MH - drug effects
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 20187900LA
- EngRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEPT - REVIEWPT -
REVIEW, TUTORIALDA - 20000504IS - 0378-4274SB - MSB - XCY - NETHERLANDSJC -
VXNAA - AuthorEM - 200007
UR - PM:0010720725
SO - Toxicol Lett
2000 Mar 15 ;112-113():153-156
13
UI - 4
AU - Parrott AC
AU - Sisk E
AU - Turner JJ
AD - Department of
Psychology, University of East London, E15 4LZ, London, UK
TI -
Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users [In Process
Citation]
AB - Twelve heavy
recreational ecstasy drug users (30-1000 occasions), 16 light ecstasy users
(1-20 occasions) and 22 non ecstasy user controls, with group mean ages around
21 years, were compared. Three self-rating questionnaires were completed when
drug-free: the SCL-90 (an outpatient psychiatric symptom checklist), the
impulsiveness venturesomeness and empathy (IVE) scale; and the uplifts,
hassles, stresses and cognitive failures questionnaire. Heavy Ecstasy users
reported significantly higher scores than controls on the following SCL-90
factors: paranoid ideation, psychoticism, somatisation, obsessionality,
anxiety, hostility, phobic anxiety, altered appetite and restless sleep,
together with greater IVE impulsiveness. Light ecstasy users generally produced
intermediate scores, with significantly higher scores than controls on two
factors and significantly lower scores than heavy ecstasy users on another two.
Previous reports have described various psychiatric and psychobiological
disorders in recreational ecstasy users, but it is not known how typical they
are, being mainly based on individual case studies. This is the first study to
describe psychological problems in a non clinical sample of young recreational
ecstasy users. However, our ecstasy users were polydrug users, with both groups
showing significantly greater usage of amphetamine, LSD and cocaine, than the
controls. These other illicit drugs probably contributed to their adverse
psychobiological profiles, while there is also the possibility of pre-existing
differences between ecstasy users and non users. However, since repeated MDMA
can cause serotonergic neurotoxicity in laboratory animals and man, these
problems may reflect reduced serotonin activity induced by regular ecstasy use
RP - NOT IN FILE
NT - UI - 20283515LA
- EngDA - 20000614IS - 0376-8716SB - MCY - IRELANDJC - EBSAA - AUTHORRO - O:099
UR - PM:0010821995
SO - Drug Alcohol
Depend 2000 Jul 1 ;60(1):105-110
14
UI - 12
AU - Ricaurte GA
AU - McCann UD
AU - Szabo Z
AU - Scheffel U
AD - Department of
Neurology, Johns Hopkins Medical Institutions, 5501 Hopkins Bayview Circle,
Baltimore, MD, USA. ricaurte@jhmi.edu
TI - Toxicodynamics
and long-term toxicity of the recreational drug, 3, 4-
methylenedioxymethamphetamine (MDMA, 'Ecstasy')
AB - The
recreational drug, (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), is
a potent serotonin (5-HT) neurotoxin in animals. Whether humans who use MDMA
incur 5-HT neural injury is unknown. The present studies utilized positron
emission tomography (PET) in conjunction with the 5-HT transporter ligand,
[11C]McN-5652 to assess the status of brain 5-HT neurons in human MDMA users.
Like nonhuman primates treated with neurotoxic doses of MDMA, humans with a
history of MDMA use showed lasting decrements in global brain [11C]McN-5652
binding, with decreases in [11C]McN-5652 binding positively correlated to the
extent of previous MDMA use. These results suggest that human MDMA use results
in brain 5-HT neurotoxicity
MH - Animal
MH - Brain
MH - drug effects
MH - metabolism
MH -
Chromatography,High Pressure Liquid
MH - Female
MH - Human
MH - Isoquinolines
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - blood
MH - pharmacology
MH - toxicity
MH - Neurons
MH - Papio
MH - Serotonin
Agents
MH - Serotonin
Antagonists
MH -
Support,U.S.Gov't,P.H.S.
MH -
Tomography,Emission-Computed
RP - NOT IN FILE
NT - UI - 20187898LA
- EngRN - 0 (Isoquinolines)RN - 0 (Serotonin Agents)RN - 0 (Serotonin
Antagonists)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
96795-90-3 (McN 5652)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALID -
DA05707/DA/NIDAID - DA06275/DA/NIDADA - 20000504IS - 0378-4274SB - MSB - XCY -
NETHERLANDSJC - VXNAA - AuthorEM - 200007
UR - PM:0010720723
SO - Toxicol Lett
2000 Mar 15 ;112-113():143-146
15
UI - 14
AU - Schroeder B
AU - Brieden S
AD - Department of
Ophthalmology, Philipps-University, Germany. schroed2@mailer.uni-marburg.de
TI - Bilateral sixth
nerve palsy associated with MDMA ("ecstasy") abuse
AB - PURPOSE:To
report the association of methylenedioxymetamphetamine (MDMA,
"ecstasy") abuse and bilateral sixth nerve palsy. METHODS: Case
report. RESULTS: A 17-year-old male presented with horizontal diplopia in all
directions of gaze after having taken MDMA tablets at 5-day to 7- day intervals
during a 2-month period. Examination showed bilateral sixth nerve palsy. Ocular
motility returned to normal within 5 days without use of MDMA and with no other
treatment. CONCLUSION: Methylenedioxymetamphetamine "ecstasy" abuse
should be considered in the differential diagnosis in otherwise unexplained
sixth nerve palsy
MH - Abducens Nerve
Diseases
MH - chemically
induced
MH - Adolescence
MH - Case Report
MH - Diplopia
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Substance-Related Disorders
MH - etiology
MH - Visual Fields
RP - NOT IN FILE
NT - UI - 20170775LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 20000404IS -
0002-9394SB - ASB - MCY - UNITED STATESJC - 3OQAA - AuthorEM - 200006
UR - PM:0010704573
SO - Am J Ophthalmol
2000 Mar ;129(3):408-409
16
UI - 7
AU - Tuchtenhagen F
AU - Daumann J
AU - Norra C
AU - Gobbele R
AU - Becker S
AU - Pelz S
AU - Sass H
AU - Buchner H
AU -
Gouzoulis-Mayfrank E
AD - Department of
Psychiatry and Psychotherapy, Medical Faculty of the University of Technology,
Pauwelsstrasse 30, D-52074, Aachen, Germany
TI - High intensity
dependence of auditory evoked dipole source activity indicates decreased
serotonergic activity in abstinent ecstasy (MDMA) users
AB - Neurotoxic
damage of central serotonergic systems has been demonstrated in numerous animal
studies after exposure to methylenedioxyamphetamines (ecstasy). A high
intensity dependence of auditory evoked potentials and, particularly, of the
tangential N1/P2 source activity has been associated with low levels of
serotonergic neurotransmission in humans. We performed an auditory evoked
potentials study in 28 abstinent recreational ecstasy users and two equally
sized groups of cannabis users and nonusers. The ecstasy users exhibited an
increase of the amplitude of the tangential N1/P2 source activity with higher
stimulus intensities; whereas, both control groups failed to exhibit this
feature. These data are in line with the hypothesis that abstinent ecstasy
users present with diminished central serotonergic activity. This feature of
information processing is probably related to the well- recognized neurotoxic
potential of ecstasy. Our data indicate that recreational ecstasy use may cause
long-term alterations in the function (and possibly structure) of the human
brain
MH - Adolescence
MH - Adult
MH - Analysis of
Variance
MH - Brain
MH - drug effects
MH - physiology
MH - Brain Mapping
MH - Evoked
Potentials,Auditory
MH - Female
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH -
Receptors,Serotonin
MH - Serotonin
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 20250716LA
- EngRN - 0 (Receptors, Serotonin)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN
- 50-67-9 (Serotonin)PT - JOURNAL ARTICLEDA - 20000602IS - 0893-133XSB - MCY -
UNITED STATESJC - ADQAA - AuthorEM - 200008
UR - PM:0010788760
SO -
Neuropsychopharmacology 2000 Jun ;22(6):608-617
17
UI - 3
AU - Wareing M
AU - Fisk JE
AU - Murphy PN
AD - Centre for
Studies in the Social Sciences, Edge Hill College of Higher Education,
Ormskirk, UK
TI - Working memory
deficits in current and previous users of MDMA ('ecstasy') [In Process
Citation]
AB - Current and
previous users of the drug MDMA ('ecstasy') were tested on measures of central
executive functioning, information processing speed, and on self-report
measures of arousal and anxiety. The results were compared with those for a
control group who did not use MDMA. Relative to the control group, both user
groups were found to be impaired in some aspects of central executive
functioning. Also, there were significant group differences on the measures of
anxiety (users were more anxious) and on arousal (previous users scoring higher
on the arousal measure relative to current users). Users processed information
as quickly as non-users but less accurately. Some possible mediators of the
above group differeces are discussed
RP - NOT IN FILE
NT - UI - 20291984LA
- EngDA - 20000530IS - 0007-1269SB - MCY - ENGLANDJC - B1SAA - AUTHORRO - O:099
UR - PM:0010832513
SO - Br J Psychol
2000 May ;91 (Pt 2)():181-188
18
UI - 22
AU - Aguirre N
AU - Barrionuevo M
AU - Ramirez MJ
AU - Del Rio J
AU - Lasheras B
AD - Department of
Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain
TI - Alpha-lipoic
acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)- induced neurotoxicity
AB - A single
administration of 3,4-methylenedioxymethamphetamine (MDMA, 20 mg/kg, i.p.),
induced significant hyperthermia in rats and reduced 5- hydroxytryptamine
(5-HT) content and [3H]paroxetine-labeled 5-HT transporter density in the
frontal cortex, striatum and hippocampus by 40-60% 1 week later. MDMA treatment
also increased glial fibrillary acidic protein (GFAP) immunoreactivity in the
hippocampus. Repeated administration of the metabolic antioxidant alpha-lipoic
acid (100 mg/kg, i.p., b.i.d. for 2 consecutive days) 30 min prior to MDMA did
not prevent the acute hyperthermia induced by the drug; however, it fully
prevented the serotonergic deficits and the changes in the glial response
induced by MDMA. These results further support the hypothesis that free radical
formation is responsible for MDMA-induced neurotoxicity
MH - Animal
MH - Antioxidants
MH - pharmacology
MH - Astrocytes
MH - drug effects
MH - metabolism
MH - Binding Sites
MH - Carrier
Proteins
MH - Fever
MH - chemically
induced
MH - Frontal Lobe
MH - cytology
MH - Glial
Fibrillary Acidic Protein
MH - analysis
MH - Hippocampus
MH - Hypothermia
MH - Male
MH - Membrane
Glycoproteins
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - antagonists
& inhibitors
MH - toxicity
MH - Neostriatum
MH - Neuroprotective
Agents
MH - Paroxetine
MH - Pyramidal Cells
MH - Rats
MH - Rats,Wistar
MH - Serotonin
MH -
Support,Non-U.S.Gov't
MH - Thioctic Acid
RP - NOT IN FILE
NT - UI - 20084683LA
- EngRN - 0 (serotonin transporter)RN - 0 (Antioxidants)RN - 0 (Carrier Proteins)RN
- 0 (Glial Fibrillary Acidic Protein)RN - 0 (Membrane Glycoproteins)RN - 0
(Neuroprotective Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 61869-08-7
(Paroxetine)RN - 62-46-4 (Thioctic Acid)PT - JOURNAL ARTICLEDA - 20000119IS -
0959-4965SB - MCY - ENGLANDJC - A6MAA - AuthorEM - 200003
UR - PM:0010619665
SO - Neuroreport
1999 Nov 26 ;10(17):3675-3680
19
UI - 18
AU - Bailly D
AD - Clinique de la
Charite, Centre Hospitalier Regional Universitaire, Lille
TI -
[Neuropsychiatric disorders induced by MDMA ("Ecstasy")]
AB - If
neurotoxicity of MDMA (ecstasy) is now well documented in animals, it is not
the same in humans. MDMA intoxication puts the problem of its possible link
with the serotonin syndrome and the neuroleptic malignant syndrome.
Neuropathological consequences following MDMA intake have been reported,
including hemorrhaging and cerebral infarction, cerebral venous sinus
thrombosis, and acute inflammatory CNS disease. However, the physiopathology of
these complications remains unclear. In the same way, there have been various
reports that have attributed MDMA to precipitating the onset of a wide range of
psychiatric disorders including sleep disorders, cognitive disorders, panic
attacks, depression, flashbacks, psychosis and severe paranoia. Findings
suggest that these psychiatric manifestations might be consequences of MDMA
induced brain serotonin neurotoxic lesions. All these data are examined from a
critical review of the literature
MH - Cerebral
Hemorrhage
MH - chemically
induced
MH - Cerebral Veins
MH - drug effects
MH - Dopamine
MH - metabolism
MH - English
Abstract
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Mental
Disorders
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Paranasal
Sinuses
MH - blood supply
MH - Serotonin
Agents
MH - Sleep Disorders
MH - Venous
Thrombosis
RP - NOT IN FILE
NT - UI - 20133782LA
- FreRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 51-61-6 (Dopamine)PT - JOURNAL
ARTICLEDA - 20000317IS - 0013-7006SB - MCY - FRANCEJC - EFBAA - AuthorEM -
200005
UR - PM:0010668603
SO - Encephale 1999
Nov ;25(6):595-602
20
UI - 31
AU - Chang L
AU - Ernst T
AU - Grob CS
AU - Poland RE
AD - Department of
Neurology, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance,
California 90502, USA. Linda_Chang@humc.edu
TI - Cerebral (1)H
MRS alterations in recreational 3, 4- methylenedioxymethamphetamine (MDMA,
"ecstasy") users
AB -
3,4-methylenedioxymethamphetamine (MDMA) is an illicit drug that has been
associated with serotonergic axonal degeneration in animals. This study
evaluates neurochemical abnormalities in recreational MDMA users. Twenty-two
MDMA users and 37 normal subjects were evaluated with magnetic resonance
imaging (MRI) and proton magnetic resonance spectroscopy ((1)H MRS) in the
mid-frontal, mid-occipital, and parietal brain regions. (1)H MRS showed normal
N-acetyl (NA) compounds in all brain regions. The myo-inositol (MI)
concentration (+16.3%, P = 0.04) and the MI to creatine (CR) ratio (+14.1%, P =
0. 01) were increased in the parietal white matter of MDMA users. The
cumulative lifetime MDMA dose showed significant effects on [MI] in the
parietal white matter and the occipital cortex. The normal NA concentration
suggests a lack of significant neuronal injury in recreational MDMA users.
However, the usage-related increase in MI suggests that exposure to MDMA, even
at recreational doses, may cause increased glial content. J. Magn. Reson.
Imaging 1999;10:521-526. Copyright 1999 Wiley-Liss, Inc
MH - Adult
MH - Aged
MH - Aged,80 and
over
MH - Aspartic Acid
MH - analogs &
derivatives
MH - analysis
MH - Brain
MH - drug effects
MH - pathology
MH - Brain Chemistry
MH - Choline
MH - Creatine
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Inositol
MH - Magnetic
Resonance Imaging
MH - Male
MH - Middle Age
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nuclear
Magnetic Resonance
MH -
Substance-Related Disorders
MH - metabolism
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 99437942LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 56-84-8 (Aspartic Acid)RN -
57-00-1 (Creatine)RN - 62-49-7 (Choline)RN - 6917-35-7 (Inositol)RN - 997-55-7
(N-acetylaspartate)PT - JOURNAL ARTICLEID - DA00280/DA/NIDAID - MO1
RR00425/RR/NCRRID - MH00534/MH/NIMHDA - 19991115IS - 1053-1807SB - MCY - UNITED
STATESJC - BEOAA - AuthorEM - 200001
UR - PM:0010508318
SO - J Magn Reson
Imaging 1999 Oct ;10(4):521-526
21
UI - 38
AU - Colado MI
AU - Granados R
AU - O'Shea E
AU - Esteban B
AU - Green AR
AD - Department of
Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain.
colado@eucmax.sim.ucm.es
TI - The acute
effect in rats of 3,4-methylenedioxyethamphetamine (MDEA, "eve") on body
temperature and long term degeneration of 5-HT neurones in brain: a comparison
with MDMA ("ecstasy")
AB - Administration
of a single dose of the recreationally used drug 3,4-
methylenedioxyethamphetamine (MDEA or "eve") to Dark Agouti rats
resulted in an acute dose-dependent hyperthermic response. The peak effect and
duration of hyperthermia of a dose of MDEA of 35 mg/kg intraperitoneally was
similar to a dose of 3,4- methylenedioxymethamphetamine (MDMA or
"ecstasy") of 15 mg/kg intraperitoneally. Seven days later this dose
of MDMA produced a marked (approximately 50%) loss of 5-HT and its metabolite
5-HIAA in cortex, hippocampus and striatum and a similar loss of
[3H]-paroxetine binding in cortex: these losses reflecting the MDMA-induced
neurotoxic degeneration of 5-HT nerve endings. In contrast, administration of
MDEA (15, 25 or 35 mg/kg), even at the highest dose, produced only a 20% loss
in cortex and hippocampus and no decrease in striatum. The neurotoxic effect of
MDEA was only weakly dose-dependent. Neither MDEA (35 mg/kg) nor MDMA (15
mg/kg) altered striatal dopamine content 7 days later. MDEA appeared to have
about half the potency of MDMA in inducing acute hyperthermia and 25% of the
potency in inducing degeneration of cerebral 5-HT neurones. However since
higher doses of MDEA (compared to MDMA) are probably necessary to induce mood
changing effects, these data do not support any contention that this compound
is a "safer" recreational drug than MDMA in terms of either acute
toxicity or long term neurodegeneration
MH - Amphetamines
MH - toxicity
MH - Animal
MH - Brain
MH - drug effects
MH - metabolism
MH - Cerebral Cortex
MH - Comparative
Study
MH - Dose-Response
Relationship,Drug
MH - Fever
MH - chemically
induced
MH - Hippocampus
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nerve Endings
MH - Paroxetine
MH - analysis
MH - Rats
MH - Serotonin
MH -
Support,Non-U.S.Gov't
MH - Time Factors
MH - Visual Cortex
MH -
3,4-Methylenedioxyamphetamine
MH - analogs &
derivatives
RP - NOT IN FILE
NT - UI - 99328154LA
- EngRN - 0 (Amphetamines)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 61869-08-7
(Paroxetine)RN - 82801-81-8 (3,4-methylenedioxyethamphetamine)PT - JOURNAL
ARTICLEDA - 19990901IS - 0901-9928SB - MCY - DENMARKJC - PHTAA - AuthorEM -
199911
UR - PM:0010401727
SO - Pharmacol
Toxicol 1999 Jun ;84(6):261-266
22
UI - 43
AU - Colado MI
AU - Esteban B
AU - O'Shea E
AU - Granados R
AU - Green AR
AD - Departamento de
Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
colado@eucmax.sim.ucm.es
TI - Studies on the
neuroprotective effect of pentobarbitone on MDMA-induced neurodegeneration
AB - Administration
of a dose of 15 mg/kg of the recreationally used drug
3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") to Dark Agouti
rats resulted in an acute hyperthermic response which was followed 7 days later
by a marked (approximately 45%) loss of 5-HT and its metabolite 5-HIAA in
cortex, hippocampus and striatum and a similar loss of [3H]-paroxetine binding
in cortex. These losses reflect the MDMA-induced neurotoxic degeneration of
5-HT nerve endings. Administration of pentobarbitone (40 mg/kg) concurrently
with MDMA produced a significant attenuation of the neurotoxic damage, but also
acute hypothermia. When the temperature of the MDMA plus pentobarbitone-
treated group was kept elevated to that of the MDMA-treated group by the use of
a homeothermic blanket, the neuroprotective effect of pentobarbitone was lost.
These data demonstrate that pentobarbitone appears to possess no intrinsic
neuroprotective activity and the previously reported activity is due to a
hypothermic action of the drug
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - Brain
MH - pathology
MH - Gaba
MH - physiology
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Neuroprotective
Agents
MH - pharmacology
MH - Paroxetine
MH - metabolism
MH - Pentobarbital
MH - Rats
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99244074LA
- EngRN - 0 (Neuroprotective Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 56-12-2 (GABA)RN - 61869-08-7
(Paroxetine)RN - 76-74-4 (Pentobarbital)PT - JOURNAL ARTICLEDA - 19990610IS -
0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199908
UR - PM:0010229068
SO -
Psychopharmacology (Berl) 1999 Mar ;142(4):421-425
23
UI - 44
AU - Colado MI
AU - O'Shea E
AU - Esteban B
AU - Granados R
AU - Green AR
AD - Departamento de
Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
colado@eucmax.sim.ucm.es
TI - In vivo
evidence against clomethiazole being neuroprotective against MDMA
('ecstasy')-induced degeneration of rat brain 5-HT nerve terminals by a free
radical scavenging mechanism
AB - Clomethiazole
is an effective neuroprotective agent against the degeneration of 5-HT neurones
that follows administration of 3,4- methylenedioxymethamphetamine (MDMA or
'ecstasy'). Since there is good evidence that free radical formation resulting
from auto-oxidation of MDMA metabolites is responsible for the degeneration we
have examined whether clomethiazole is a free radical scavenger. MDMA (15 mg/kg
i.p.) increased the formation of 2,3- and 2,5-dihydroxybenzoic acids (2,3- DHBA
and 2,5-DHBA) from salicylic acid perfused through a microdialysis tube
implanted in the hippocampus, indicating increased free radical formation.
Clomethiazole (50 mg/kg i.p.) administered 5 min prior and 55 min post MDMA
prevented both the acute MDMA-induced hyperthermia and the rise in 2,3- and
2,5-DHBA. However, when the temperature of the MDMA + clomethiazole treated
rats was kept elevated to that of the MDMA treated rats with a homeothermic
blanket there was no inhibition of the MDMA-induced increase in 2,3-DHBA or
2,5-DHBA. These data suggest firstly that free radical formation is inhibited
when the acute MDMA- induced hyperthermia is prevented. Secondly the data
further indicate that clomethiazole has no free radical scavenging activity
since the drug produces substantial neuroprotection when MDMA + clomethiazole
treated rats are kept hyperthermic. This conclusion was strengthened by our
observation that clomethiazole is a weak inhibitor (IC50 > 1 mM) of lipid
peroxidation in synaptosomes when it had been induced by addition of FeCl2 +
ascorbic acid
MH - Animal
MH -
Biotransformation
MH - Body
Temperature
MH - drug effects
MH - Brain
MH - metabolism
MH - Cerebral Cortex
MH - Chlormethiazole
MH - pharmacology
MH - Corpus Striatum
MH - Free Radical
Scavengers
MH - Hippocampus
MH - Hydroxybenzoic
Acids
MH -
Hydroxyindoleacetic Acid
MH - Kinetics
MH - Male
MH - Microdialysis
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Nerve
Degeneration
MH - chemically
induced
MH - pathology
MH - prevention
& control
MH - Nerve Endings
MH - Neuroprotective
Agents
MH - Paroxetine
MH -
pharmacokinetics
MH - Rats
MH - Salicylic Acid
MH - Serotonin
MH - Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99233241LA
- EngRN - 0 (Free Radical Scavengers)RN - 0 (Hydroxybenzoic Acids)RN - 0
(Neuroprotective Agents)RN - 303-38-8 (2-pyrocatechuic acid)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 490-79-9 (2,5-dihydroxybenzoic
acid)RN - 50-67-9 (Serotonin)RN - 533-45-9 (Chlormethiazole)RN - 54-16-0
(Hydroxyindoleacetic Acid)RN - 61869-08-7 (Paroxetine)RN - 69-72-7 (Salicylic
Acid)PT - JOURNAL ARTICLEDA - 19990624IS - 0028-3908SB - MCY - ENGLANDJC -
NZBAA - AuthorEM - 199908
UR - PM:0010218873
SO -
Neuropharmacology 1999 Feb ;38(2):307-314
24
UI - 51
AU - Colado MI
AU - O'Shea E
AU - Granados R
AU - Esteban B
AU - Martin AB
AU - Green AR
AD - Departamento de
Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
TI - Studies on the
role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark
Agouti rats following 3,4- methylenedioxymethamphetamine (MDMA or 'ecstasy')
administration
AB - 1. We
investigated whether dopamine plays a role in the neurodegeneration of
5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain
after 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administration. 2.
Haloperidol (2 mg kg(-1) i.p.) injected 5 min prior and 55 min post MDMA (15 mg
kg(-1) i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the
neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA +
haloperidol treated rats was kept elevated, this protective effect was
marginal. 3. MDMA (15 mg kg(-1)) increased the dopamine concentration in the
dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg(-1)
i.p., plus benserazide, 6.25 mg kg(-1) i.p.) injected 2 h after MDMA (15 mg
kg(-1)) enhanced the increase in dopamine in the dialysate, but subsequent
neurodegeneration was unaltered. L-DOPA (25 mg kg(-1)) injected before a
sub-toxic dose of MDMA (5 mg kg(-1)) failed to induce neurodegeneration. 4. The
MDMA-induced increase in free radical formation in the hippocampus (indicated
by increased 2,3- and 2,5- dihydroxybenzoic acid in a microdialysis probe
perfused with salicylic acid) was unaltered by L-DOPA. 5. The neuroprotective
drug clomethiazole (50 mg kg(-1) i.p.) did not influence the MDMA-induced
increase in extracellular dopamine. 6. These data suggest that previous
observations on the protective effect of haloperidol and potentiating effect of
L-DOPA on MDMA-induced neurodegeneration may have resulted from effects on
MDMA-induced hyperthermia. 7. The increased extracellular dopamine
concentration following MDMA may result from effects of MDMA on dopamine
re-uptake, monoamine oxidase and 5-HT release rather than an 'amphetamine-like'
action on dopamine release, thus explaining why the drug does not induce
degeneration of dopamine nerve endings
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - Brain
MH - metabolism
MH - Dopamine
MH - physiology
MH - Free Radicals
MH - Haloperidol
MH - pharmacology
MH - Levodopa
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH -
Neurodegenerative Diseases
MH - chemically
induced
MH - Paroxetine
MH - Rats
MH - Serotonin
MH - analysis
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99208114LA
- EngRN - 0 (Free Radicals)RN - 0 (Levodopa)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6
(Dopamine)RN - 52-86-8 (Haloperidol)RN - 61869-08-7 (Paroxetine)PT - JOURNAL
ARTICLEDA - 19990525IS - 0007-1188SB - MCY - ENGLANDJC - B00AA - AuthorEM -
199907
UR - PM:0010193771
SO - Br J Pharmacol
1999 Feb ;126(4):911-924
25
UI - 36
AU - Dafters RI
AU - Duffy F
AU - O'Donnell PJ
AU - Bouquet C
AD - Psychology
Department, Glasgow University, UK. dick@psy.gla.ac.uk
TI - Level of use of
3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) in humans correlates with
EEG power and coherence
AB - RATIONALE:
Despite animal studies implicating 3,4- methylenedioxymethamphetamine (MDMA or
Ecstasy) in serotonergic neurotoxicity, there is little direct evidence of
changes in neural function in humans who use MDMA as a recreational drug.
OBJECTIVE: The present study investigated whether there is a correlation
between quantitative EEG variables (spectral power and coherence) and
cognitive/mood variables, and level of prior use of MDMA. METHODS: Twenty-three
recreational MDMA users were studied. Resting EEG was recorded with eyes
closed, using a 128-electrode geodesic net system, from which spectral power,
peak frequency and coherence levels were calculated. Tests of intelligence (NART),
immediate and delayed memory, frontal function (card sort task), and mood (BDI
and PANAS scales) were also administered. Pearson correlation analyses were
used to examine the relationship between these measures and the subject's
consumption of MDMA during the previous 12-month period. Partial correlation
was used to control for the use of other recreational drugs. RESULTS: MDMA use
was positively correlated with absolute power in the alpha (8-12 Hz) and beta
(12-20 Hz) frequency bands, but not with the delta (1-3 Hz) or theta (4-7 Hz)
bands. MDMA use was negatively correlated with EEG coherence, a measure of
synchrony between paired cortical locations, in posterior brain sites thought
to overly the main visual association pathways of the occipito-parietal region.
MDMA use did not correlate significantly with any of the mood/cognitive
measures except the card sort task, with which it was weakly negatively
correlated. CONCLUSIONS: Alpha power has been shown to be inversely related to
mental function and has been used as an indirect measure of brain activation in
both normal and abnormal states. Reduced coherence levels have been associated
with dysfunctional connectivity in the brain in disorders such as dementia,
white-matter disease and normal aging. Our results may indicate altered brain
function correlated with prior MDMA use, and show that electroencephalography
may be a cheap and effective tool for examining neurotoxic effects of MDMA and
other drugs
MH - Adolescence
MH - Adult
MH - Affect
MH - drug effects
MH - Alpha Rhythm
MH - Cognition
MH -
Electroencephalography
MH - Hallucinogens
MH - administration
& dosage
MH - adverse effects
MH - pharmacology
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Street Drugs
MH -
Substance-Related Disorders
MH - diagnosis
RP - NOT IN FILE
NT - UI - 99372548LA
- EngRN - 0 (Hallucinogens)RN - 0 (Street Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19990914IS -
0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199911
UR - PM:0010445376
SO -
Psychopharmacology (Berl) 1999 Jul ;145(1):82-90
26
UI - 57
AU - de la TR
AU - Ortuno J
AU - Mas M
AU - Farre M
AU - Segura J
TI - Fatal MDMA
intoxication [letter; comment]
MH - Anti-HIV Agents
MH - poisoning
MH - Cytochrome
P-450 CYP2D6
MH - metabolism
MH - Drug
Interactions
MH - Hallucinogens
MH -
pharmacokinetics
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Ritonavir
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99151468LA
- EngRN - EC 1.14.99.- (Cytochrome P-450 CYP2D6)RN - 0 (Anti-HIV Agents)RN - 0
(Hallucinogens)RN - 0 (Ritonavir)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - COMMENTPT - LETTERDA - 19990311IS
- 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM - 199905RO - M:LC1
UR - PM:0010029010
SO - Lancet 1999 Feb
13 ;353(9152):593
27
UI - 28
AU - Fineschi V
AU - Centini F
AU - Mazzeo E
AU - Turillazzi E
AD - Unit of Legal
Medicine, University of Bari, Italy. vfinesc@tin.it
TI - Adam (MDMA) and
Eve (MDEA) misuse: an immunohistochemical study on three fatal cases
AB - Three fatal
cases of MDMA/MDEA misuse have been examined. These referred to white males
between 19 and 20 years of age, in which post- mortem toxicology showed the
presence of MDMA (in one case), MDEA (in one case) and both (in one case). The
clinical data were analysed and the histopathological findings were studied
following immunohistochemical investigations. A complete immunohistochemical
study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with
alterations of the organs typical of a DIC. Clinical, histopathological and
toxicological data suggest that severe or fatal complications following ecstasy
ingestion could be related to idiosyncratic response
MH - Adult
MH - Case Report
MH - Disseminated
Intravascular Coagulation
MH - chemically
induced
MH - pathology
MH - therapy
MH - Fatal Outcome
MH - Forensic
Medicine
MH - Hallucinogens
MH - chemistry
MH - poisoning
MH - Human
MH - Male
MH - Mass
Fragmentography
MH - Myoglobinuria
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rhabdomyolysis
MH -
3,4-Methylenedioxyamphetamine
MH - analogs &
derivatives
RP - NOT IN FILE
NT - UI - 20003472LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 82801-81-8
(3,4-methylenedioxyethamphetamine)PT - JOURNAL ARTICLEDA - 19991130IS -
0379-0738SB - MCY - IRELANDJC - F49AA - AuthorEM - 200002
UR - PM:0010533279
SO - Forensic Sci
Int 1999 Sep 30 ;104(1):65-74
28
UI - 34
AU - Gijsman HJ
AU - Verkes RJ
AU - van Gerven JM
AU - Cohen AF
TI - MDMA study
[letter; comment]
MH - Animal
MH - Clinical Trials
MH - standards
MH - Ethics,Medical
MH - Hallucinogens
MH - adverse effects
MH - toxicity
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neurons
MH - drug effects
MH - metabolism
MH - pathology
MH -
Receptors,Serotonin
MH - Serotonin
RP - NOT IN FILE
NT - UI - 99411457LA
- EngRN - 0 (Hallucinogens)RN - 0 (Receptors, Serotonin)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - COMMENTPT
- LETTERDA - 19991008IS - 0893-133XSB - MCY - UNITED STATESJC - ADQEM -
199912RO - M:LC2
UR - PM:0010481843
SO -
Neuropsychopharmacology 1999 Oct ;21(4):597
29
UI - 15
AU -
Gouzoulis-Mayfrank E
AU - Hermle L
AU - Kovar KA
AU - Sass H
TI - [Comment on R.
Thomasius, M. Schmolke, D. Kraus: MDMA ("Ecstasy") use-- an overview
of psychiatric and medical sequelae (letter; comment)]
MH - Drug
Contamination
MH - Hallucinogens
MH - adverse effects
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Substance-Related Disorders
MH - diagnosis
RP - NOT IN FILE
NT - UI - 20147377LA
- GerRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - COMMENTPT - LETTERDA - 20000324IS
- 0720-4299SB - MCY - GERMANYJC - F67EM - 200006RO - M:CNR
UR - PM:0010683753
SO - Fortschr Neurol
Psychiatr 1999 Dec ;67(12):574-576
30
UI - 29
AU - Harrington RD
AU - Woodward JA
AU - Hooton TM
AU - Horn JR
AD - Department of
Medicine, School of Medicine, University of Washington, Seattle, USA.
rdh@u.washington.edu
TI -
Life-threatening interactions between HIV-1 protease inhibitors and the illicit
drugs MDMA and gamma-hydroxybutyrate
AB - Human
immunodeficiency virus 1 (HIV-1) protease inhibitors have dramatically reduced
the morbidity and mortality due to HIV-1 infection. However, most of these
antiretrovirals are also potent inhibitors (and occasionally inducers) of
hepatic and intestinal cytochrome P450 systems and, therefore, have the
potential to alter the elimination of any substance that utilizes these metabolic
pathways. We describe a patient infected with HIV-1 who was treated with
ritonavir and saquinavir and then experienced a prolonged effect from a small
dose of methylenedioxymetamphetamine (MDMA or ecstacy) and a nearly fatal
reaction from a small dose of gamma-hydroxybutyrate (GHB). We also discuss the
potential for HIV-1 protease inhibitors to alter the metabolism of other
abusable prescribed and illicit substances
MH - Acquired
Immunodeficiency Syndrome
MH - drug therapy
MH - Adrenergic
Uptake Inhibitors
MH - adverse effects
MH - Adult
MH - Anesthetics
MH - Case Report
MH - Drug Synergism
MH - Hallucinogens
MH - Human
MH - HIV Protease
Inhibitors
MH - pharmacology
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Ritonavir
MH - Saquinavir
MH - Sodium Oxybate
RP - NOT IN FILE
NT - UI - 99454424LA
- EngRN - 0 (Adrenergic Uptake Inhibitors)RN - 0 (Anesthetics)RN - 0
(Hallucinogens)RN - 0 (HIV Protease Inhibitors)RN - 0 (Ritonavir)RN -
127779-20-8 (Saquinavir)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN
- 502-85-2 (Sodium Oxybate)PT - JOURNAL ARTICLEDA - 19991027IS - 0003-9926SB -
ASB - MSB - XCY - UNITED STATESJC - 7FSAA - AuthorEM - 200001
UR - PM:0010527300
SO - Arch Intern Med
1999 Oct 11 ;159(18):2221-2224
31
UI - 30
AU - Hensley D
AU - Cody JT
AD - Clinical
Research Squadron, Wilford Hall Medical Center, Lackland AFB, Texas 78236-5319,
USA
TI - Simultaneous
determination of amphetamine, methamphetamine, methylenedioxyamphetamine (MDA),
methylenedioxymethamphetamine (MDMA), and methylenedioxyethylamphetamine (MDEA)
enantiomers by GC-MS
AB - A method is
described for the simultaneous determination of the ratio of l- and
d-enantiomers of amphetamine, methamphetamine, 3,4- methylenedioxyamphetamine
(MDA), 3,4-methylenedioxymethamphetamine (MDMA), and
3,4-methylenedioxyethylamphetamine (MDEA) in urine. The assay uses
liquid-liquid extraction followed by derivatization with
trifluoroacetyl-l-prolyl chloride (l-TPC) and analysis by gas
chromatography-mass spectrometry. The assay was developed using prepared
samples containing varying concentrations of each of the analytes over a range
of percentages of each enantiomer. Results showed the method to provide
accurate and reliable results in samples containing > or = 10 ng/mL
amphetamine and methamphetamine and > or = 25 ng/mL MDA, MDMA, and MDEA. The
assay was used to analyze urine samples from subjects of a controlled MDMA
study. Results for each of the eight subjects showed a greater percentage of
the l-enantiomer of MDMA initially, and the percentage increased with time
postdose. Analysis of the metabolite MDA revealed that the proportion of d-
enantiomer was initially greater than the l-enantiomer followed by a gradual
increase in the proportion of l-enantiomer until it exceeded the amount of the
d-enantiomer. In all cases, the l-MDA exceeded the d- MDA within the first 36 h
postdose
MH - Amphetamines
MH - urine
MH - Central Nervous
System Stimulants
MH - Human
MH - In Vitro
MH - Mass
Fragmentography
MH - Methamphetamine
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Sensitivity and
Specificity
MH - Stereoisomerism
MH - Substance Abuse
Detection
MH - methods
MH - Time Factors
MH - chemistry
MH -
3,4-Methylenedioxyamphetamine
MH - analogs &
derivatives
RP - NOT IN FILE
NT - UI - 99445148LA
- EngRN - 0 (Amphetamines)RN - 0 (Central Nervous System Stimulants)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 537-46-2 (Methamphetamine)RN - 82801-81-8
(3,4-methylenedioxyethamphetamine)PT - JOURNAL ARTICLEDA - 19991201IS -
0146-4760SB - MCY - UNITED STATESJC - K4RAA - AuthorEM - 200002
UR - PM:0010517560
SO - J Anal Toxicol
1999 Oct ;23(6):518-523
32
UI - 58
AU - Holland J
TI - Positron
emission tomography findings in heavy users of MDMA [letter; comment]
MH - Brain
MH - drug effects
MH - radionuclide
imaging
MH - Hallucinogens
MH - adverse effects
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Tomography,Emission-Computed
RP - NOT IN FILE
NT - UI - 99151467LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - COMMENTPT - LETTERDA - 19990311IS
- 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM - 199905RO - M:LC1
UR - PM:0010029009
SO - Lancet 1999 Feb
13 ;353(9152):592-593
33
UI - 45
AU - Jansen KL
AU - Forrest AR
TI - Toxic effect of
MDMA on brain serotonin neurons [letter; comment]
MH - Brain
MH - drug effects
MH - Cocaine
MH - adverse effects
MH - Comparative
Study
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Patient
Selection
MH - Serotonin
MH - metabolism
MH - Serotonin
Agents
MH - Vasoconstrictor
Agents
RP - NOT IN FILE
NT - UI - 99231457LA
- EngRN - 0 (Serotonin Agents)RN - 0 (Vasoconstrictor Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-36-2 (Cocaine)RN - 50-67-9
(Serotonin)PT - COMMENTPT - LETTERDA - 19990513IS - 0140-6736SB - ASB - MSB -
XCY - ENGLANDJC - L0SEM - 199907RO - M:LC2
UR - PM:0010217105
SO - Lancet 1999 Apr
10 ;353(9160):1270-1271
34
UI - 55
AU - Jansen KL
AD - The Maudsley
Hospital, Denmark Hill, London, UK. k@btinternet.com
TI - Ecstasy (MDMA)
dependence
AB - Methylenedioxymethamphetamine
(MDMA) is generally described as non- addictive. However, this report describes
three cases in which criteria for dependence were met. A wider understanding
that MDMA can be addictive in rare cases is important as very heavy use may cause
lasting neuronal changes. This risk could be reduced with effective
identification and treatment of dependent persons. In one case dependence was
linked with self-medication of post-traumatic stress disorder (PTSD)
MH - Adult
MH - Case Report
MH - Hallucinogens
MH - adverse effects
MH - therapeutic use
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Seizures
MH - chemically
induced
MH - Self Medication
MH - Stress
Disorders,Post-Traumatic
MH - drug therapy
MH -
Substance-Related Disorders
MH - diagnosis
RP - NOT IN FILE
NT - UI - 99179774LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19990806IS -
0376-8716SB - MCY - IRELANDJC - EBSAA - AuthorEM - 199910
UR - PM:0010080038
SO - Drug Alcohol
Depend 1999 Jan 7 ;53(2):121-124
35
UI - 52
AU - Jones AL
AU - Simpson KJ
AD - Guy's and St
Thomas' Hospital NHS Trust, Medical Toxicology Unit, London, UK
TI - Review article:
mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine
intoxications
AB - The social use
of ecstasy (methylenedioxymethampheta-mine, MDMA) and amphetamines is
widespread in the UK and Europe, and they are popularly considered as 'safe'.
However, deaths have occurred and hepatotoxicity has featured in many cases of
intoxication with amphetamine or its methylenedioxy analogues such as ecstasy.
Recreational use of these drugs presents an important but often concealed cause
of hepatitis or acute liver failure, particularly in young people. The patterns
of liver damage and multiple putative mechanisms of injury are discussed.
Recognition of the aetiological agent requires a high index of suspicion.
Optimum management of the resultant liver damage, including the controversial
role of liver transplantation for fulminant hepatic failure, is also discussed
MH - Amphetamine
MH - poisoning
MH - Human
MH - Liver
MH - drug effects
MH - pathology
MH - Liver
Transplantation
MH -
N-Methyl-3,4-methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 99203776LA
- EngRN - 300-62-9 (Amphetamine)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEPT - REVIEWPT -
REVIEW, TUTORIALDA - 19990414IS - 0269-2813SB - MCY - ENGLANDJC - A5DAA -
AuthorEM - 199906
UR - PM:0010102941
SO - Aliment
Pharmacol Ther 1999 Feb ;13(2):129-133
36
UI - 46
AU - Klugman A
AU - Hardy S
AU - Baldeweg T
AU - Gruzelier J
TI - Toxic effect of
MDMA on brain serotonin neurons [letter; comment]
MH - Adult
MH - Cognition
MH - drug effects
MH - Human
MH - Memory
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Psychological
Tests
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 99231456LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT
- CLINICAL TRIALPT - COMMENTPT - CONTROLLED CLINICAL TRIALPT - LETTERDA -
19990513IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM - 199907RO -
M:LC2
UR - PM:0010217104
SO - Lancet 1999 Apr
10 ;353(9160):1269-1270
37
UI - 47
AU - Kuikka JT
AU - Ahonen AK
TI - Toxic effect of
MDMA on brain serotonin neurons [letter; comment]
MH - Binding Sites
MH - drug effects
MH - Brain
MH - Human
MH - Ligands
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH -
pharmacokinetics
MH - Serotonin
MH - metabolism
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 99231455LA
- EngRN - 0 (Ligands)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - COMMENTPT
- LETTERDA - 19990513IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM -
199907RO - M:LC2
UR - PM:0010217103
SO - Lancet 1999 Apr
10 ;353(9160):1269-1
38
UI - 27
AU - Lavelle A
AU - Honner V
AU - Docherty JR
AD - Department of
Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen's Green,
Dublin 2, Ireland
TI - Investigation
of the prejunctional alpha2-adrenoceptor mediated actions of MDMA in rat atrium
and vas deferens
AB - 1. We have
investigated the effects of methylenedioxymethamphetamine (MDMA, 'ecstasy') on
peripheral noradrenergic neurotransmission in the rat. 2. In rat atrial slices
pre-incubated with [3H]-noradrenaline and in the presence of desipramine (1
micronM) to prevent effects of MDMA on basal outflow of tritium, MDMA (10
micronM) significantly inhibited the release of tritium evoked by short trains
of six pulses at 100 Hz every 10 s for 3 min. This effect did not occur in the
presence of the alpha2-adrenoceptor antagonist yohimbine (1 micronM). 3. In
epididymal portions of rat vas deferens in the presence of nifedipine (10
micronM), MDMA produced a concentration-dependent inhibition of single pulse
nerve stimulation-evoked contractions with a pD2 of 5.88+/-0.16 (n=4).
Inhibitory effects of MDMA were antagonized by the alpha2- adrenoceptor
antagonist yohimbine (0.3 micronM), but not by the 5- hydroxytryptamine
receptor antagonist cyanopindolol in a concentration (1 micronM) which markedly
antagonized the inhibitory actions of the 5- HT-1 receptor agonist
5-carboxamidotryptamine. 4. In prostatic portions of rat vas deferens in the
presence of cocaine (3 micronM), MDMA produced a concentration-dependent
inhibition of single pulse nerve stimulation-evoked contractions with a pD2 of
5. 12+/-0.21 (n=4). In the absence of cocaine, only the highest concentration
of MDMA (30 micronM) produced an inhibition, but the alpha2-adrenoceptor
antagonist yohimbine (0.3 micronM) converted the response to MDMA from
inhibition to potentiation of the stimulation-evoked contraction. 5. In
radioligand binding studies, MDMA showed similar affinities for alpha2B,
alpha2C and alpha2D-adrenoceptor sites, with pKi values of 5.14+/-0.16,
5.11+/-0. 05 and 5.31+/-0.14, respectively. 6 It is concluded that MDMA has
significant alpha2-adrenoceptor agonist actions
MH - Adrenergic
Uptake Inhibitors
MH - pharmacology
MH - Animal
MH - Cocaine
MH - Dopamine Uptake
Inhibitors
MH - Electric
Stimulation
MH -
Electrophysiology
MH - Epididymis
MH - drug effects
MH - innervation
MH - Heart Atrium
MH - In Vitro
MH - Kidney
MH - Ligands
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neuromuscular
Junction
MH - Prostate
MH - Radioligand
Assay
MH - Rats
MH - Rats,Wistar
MH -
Receptors,Adrenergic,alpha-2
MH - Submandibular
Gland
MH -
Support,Non-U.S.Gov't
MH - Vas Deferens
RP - NOT IN FILE
NT - UI - 20025573LA
- EngRN - 0 (Adrenergic Uptake Inhibitors)RN - 0 (Dopamine Uptake Inhibitors)RN
- 0 (Ligands)RN - 0 (Receptors, Adrenergic, alpha-2)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN
- 50-36-2 (Cocaine)PT - JOURNAL ARTICLEDA - 20000124IS - 0007-1188SB - MCY -
ENGLANDJC - B00AA - AuthorEM - 200003
UR - PM:0010556934
SO - Br J Pharmacol
1999 Nov ;128(5):975-980
39
UI - 54
AU - Lin HQ
AU - Burden PM
AU - Christie MJ
AU - Johnston GA
AD - Department of
Pharmacology, The University of Sydney, NSW, Australia
TI - The
anxiogenic-like and anxiolytic-like effects of MDMA on mice in the elevated
plus-maze: a comparison with amphetamine
AB - Many abused
substances have been found to possess anxiogenic-like or/and anxiolytic-like
properties. Discrepancies about the effects of MDMA, one of the most popular
recreational drugs in recent years, on anxiety have been seen in the
literature, and almost all of the data in this respect were derived from
retrospective studies. The present study was thus designed to examine the
drug's actions by using an animal model of anxiety, the elevated plus-maze test
in male mice. Intraperitoneal MDMA at 1 mg/kg was ineffective, at 4 mg/kg
decreased the percent of open arm entries (p < 0.01), and increased enclosed
entries (p < 0.05), at 12 mg/kg had no significant effect, and at 20 mg/kg
induced an increase of percent of open time (p < 0.01). As control drugs, amphetamine
(0.5-4 mg/kg, i.p.) produced a dose- dependent, anxiogenic-like effect and
diazepam (1 mg/kg, i.p.) induced an anxiolytic-like effect in the test. The
results indicate that MDMA has anxiogenic-like properties at lower doses and
anxiolytic-like at higher doses. The effects of MDMA and amphetamine on the
mouse's responses to the plus-maze are compared. These findings provide a
possible explanation for the controversies over MDMA's effects on anxiety in
the literature
MH - Amphetamine
MH - pharmacology
MH - Animal
MH - Anti-Anxiety
Agents
MH - Anti-Anxiety
Agents,Benzodiazepine
MH - Anxiety
MH - chemically
induced
MH - psychology
MH - Behavior,Animal
MH - drug effects
MH - Comparative
Study
MH - Diazepam
MH - Dopamine Uptake
Inhibitors
MH - Dose-Response
Relationship,Drug
MH - Hallucinogens
MH - Male
MH - Mice
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99178315LA
- EngRN - 0 (Anti-Anxiety Agents)RN - 0 (Anti-Anxiety Agents, Benzodiazepine)RN
- 0 (Dopamine Uptake Inhibitors)RN - 0 (Hallucinogens)RN - 300-62-9
(Amphetamine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
439-14-5 (Diazepam)PT - JOURNAL ARTICLEDA - 19990517IS - 0091-3057SB - MCY -
UNITED STATESJC - P3QAA - AuthorEM - 199907
UR - PM:0010080230
SO - Pharmacol
Biochem Behav 1999 Mar ;62(3):403-408
40
UI - 32
AU - Malpass A
AU - White JM
AU - Irvine RJ
AU - Somogyi AA
AU - Bochner F
AD - Department of
Clinical & Experimental Pharmacology, University of Adelaide, SA, Australia
TI - Acute toxicity
of 3,4-methylenedioxymethamphetamine (MDMA) in Sprague- Dawley and Dark Agouti
rats
AB - Ingestion of
MDMA ("ecstasy") by humans can cause acute toxicity manifested by
hyperthermia and death. Demethylenation of MDMA is catalyzed by cytochrome
P-450 2D6 (CYP2D6) and cytochrome P-450 2D1 (CYP2D1) in humans and rats,
respectively, and is polymorphically expressed. It has been proposed that CYP2D6
deficiency may account for the unexplained toxicity of MDMA. The female Dark
Agouti rat is deficient in CYP2D1, and serves as a model for the human poor
metabolizer. We investigated thermogenic and locomotor actions of MDMA in adult
female Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats. MDMA (2, 5, and 10
mg/kg) and saline were injected subcutaneously at ambient temperatures of 22
and 31 degrees C. There was no difference in core temperature responses between
the two rat strains. Hypothermia occurred in the first 30 min and temperature
elevation thereafter. MDMA increased locomotor activity in Sprague-Dawley but
not in Dark Agouti rats. However, MDMA had pronounced lethal effects at 31
degrees C ambient in the Dark Agouti rats only. We conclude that the poor
metaboliser phenotype may predispose to lethality, but the mechanism is as yet
unknown
MH - Animal
MH - Body
Temperature Regulation
MH - drug effects
MH - Comparative
Study
MH - Cytochrome
P-450
MH - metabolism
MH - Cytochrome
P-450 CYP2D6
MH - Female
MH - Hallucinogens
MH - toxicity
MH - Motor Activity
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Species
Specificity
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99423185LA
- EngRN - EC 1.14.99.- (Cytochrome P-450 CYP2D6)RN - 0 (cytochrome P-450
CYP2D1)RN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 9035-51-2 (Cytochrome P-450)PT -
JOURNAL ARTICLEDA - 19991021IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA -
AuthorEM - 199912
UR - PM:0010494994
SO - Pharmacol
Biochem Behav 1999 Sep ;64(1):29-34
41
UI - 39
AU - Marston HM
AU - Reid ME
AU - Lawrence JA
AU - Olverman HJ
AU - Butcher SP
AD - Fujisawa
Institute of Neuroscience, Department of Pharmacology, University of Edinburgh,
UK. Hugh.Marston@ed.ac.uk
TI - Behavioural
analysis of the acute and chronic effects of MDMA treatment in the rat
AB - RATIONALE: A
variety of animal models have shown MDMA (3,4- methylenedioxymethamphetamine)
to be a selective 5-HT neurotoxin, though little is known of the long-term
behavioural effects of the pathophysiology. The widespread recreational use of
MDMA thus raises concerns over the long-term functional sequelae in humans.
OBJECTIVE: This study was designed to explore both the acute- and
post-treatment consequences of a 3-day neurotoxic exposure to MDMA in the rat,
using a variety of behavioural paradigms. METHODS: Following training to
pretreatment performance criteria, animals were treated twice daily with
ascending doses of MDMA (10, 15, 20 mg/kg) over 3 days. Body temperature,
locomotor activity, skilled paw-reaching ability and performance of the delayed
non-match to place (DNMTP) procedure was assessed daily during this period and
on an intermittent schedule over the following 16 days. Finally, post mortem
biochemical analyses of [3H] citalopram binding and monoamine levels were
performed. RESULTS: During the MDMA treatment period, an acute 5-HT-like
syndrome was observed which showed evidence of tolerance. Once drug treatment
ceased the syndrome abated completely. During the post-treatment phase, a
selective, delay-dependent, deficit in DNMTP performance developed. Post-mortem
analysis confirmed reductions in markers of 5-HT function, in cortex,
hippocampus and striatum. CONCLUSIONS: These results confirm that acutely MDMA
exposure elicits a classical 5-HT syndrome. In the long-term, exposure results
in 5-HT neurotoxicity and a lasting cognitive impairment. These results have
significant implications for the prediction that use of MDMA in humans could
have deleterious long- term neuropsychological/psychiatric consequences
MH - Animal
MH - Behavior,Animal
MH - drug effects
MH - Biogenic
Monoamines
MH - metabolism
MH -
Chromatography,High Pressure Liquid
MH - Citalopram
MH - Kinetics
MH - Male
MH - Mental
Disorders
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - Radioligand
Assay
MH - Rats
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99306294LA
- EngRN - 0 (Biogenic Monoamines)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 59729-33-8 (Citalopram)PT -
JOURNAL ARTICLEDA - 20000112IS - 0033-3158SB - MCY - GERMANYJC - QGIAA -
AuthorEM - 200003
UR - PM:0010379626
SO -
Psychopharmacology (Berl) 1999 May ;144(1):67-76
42
UI - 41
AU - McCann UD
AU - Mertl M
AU - Eligulashvili V
AU - Ricaurte GA
AD - Unit on
Anxiety, Biological Psychiatry Branch, NIMH, Bethesda, MD 20892- 1272, USA.
umccann@helix.nih.gov
TI - Cognitive
performance in (+/-) 3,4-methylenedioxymethamphetamine (MDMA,
"ecstasy") users: a controlled study
AB - RATIONALE:
(+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is an
amphetamine analog and drug of abuse. In animals, MDMA damages brain serotonin
(5-HT) neurons at doses that overlap with those used recreationally by some
humans. To date, few functional sequelae of MDMA- induced 5-HT damage have been
identified. OBJECTIVE: Since serotonin is thought to be involved in cognitive
processes, and since previous studies have reported verbal and visual memory
deficits in MDMA users, the present study sought to determine whether other
cognitive processes are influenced by previous exposure to MDMA. METHODS:
Twenty-two MDMA users who had not used MDMA for at least 3 weeks and 23 control
subjects were tested repeatedly with a computerized cognitive performance
assessment battery while participating in a 5-day controlled inpatient study.
Cerebrospinal fluid (CSF) measures of monoamine metabolites were also collected
as an index of brain monoaminergic function. RESULTS: MDMA users and controls
were found to perform similarly on several cognitive tasks. However, MDMA
subjects had significant performance deficits on a sustained attention task
requiring arithmetic calculations, a task requiring complex attention and
incidental learning, a task requiring short term memory and a task of semantic
recognition and verbal reasoning. MDMA users also had significant selective
decreases in CSF 5-HIAA. CONCLUSIONS: The present CSF data provide further
evidence that MDMA is neurotoxic to brain 5-HT neurons in humans, and the
behavioral data suggest that brain 5-HT injury is associated with subtle, but
significant, cognitive deficits
MH - Adult
MH - Analysis of
Variance
MH - Attention
MH - drug effects
MH - Cognition
MH - Female
MH - Hallucinogens
MH - pharmacology
MH - Human
MH - Hydroxyindoleacetic
Acid
MH - cerebrospinal
fluid
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neurons
MH - Recall
MH -
Support,U.S.Gov't,P.H.S.
MH - Task
Performance and Analysis
RP - NOT IN FILE
NT - UI - 99293980LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 54-16-0 (Hydroxyindoleacetic
Acid)PT - JOURNAL ARTICLEID - DA05707/DA/NIDAID - DA05938/DA/NIDAID -
DA00206/DA/NIDADA - 19990805IS - 0033-3158SB - MCY - GERMANYJC - QGIAA -
AuthorEM - 199910
UR - PM:0010367560
SO -
Psychopharmacology (Berl) 1999 Apr ;143(4):417-425
43
UI - 25
AU - McCann UD
AU - Eligulashvili V
AU - Mertl M
AU - Murphy DL
AU - Ricaurte GA
AD - Biological
Psychiatry Branch, National Institute of Mental Health, Bethesda, MD
20892-1272, USA. umccann@helix.nih.gov
TI - Altered
neuroendocrine and behavioral responses to m- chlorophenylpiperazine in
3,4-methylenedioxymethamphetamine (MDMA) users
AB - RATIONALE:
(+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a
popular drug of abuse and a brain serotonin neurotoxin in animals. Growing
evidence indicates that humans are also susceptible to MDMA's neurotoxic
effects, although few functional consequences of MDMA- induced 5-HT damage have
been identified. OBJECTIVE: The present study sought to determine whether
possible differences between MDMA users and control subjects could be unmasked
by utilizing a pharmacological challenge with the mixed 5-HT agonist,
meta-chlorophenylpiperazine (m- CPP). It was postulated that 5-HT neurotoxicity
in MDMA users would be associated with altered 5-HT responsivity, exemplified
by altered physiological and behavioral responses to m-CPP. METHODS: Twenty-five
MDMA users who had not taken MDMA for at least 3 weeks and 25 controls received
intravenous placebo (normal saline) and m-CPP (0.08 mg/kg) in a fixed order,
single blind design. Repeated measures of mood, physical symptoms, and blood
samples for neuroendocrine analyses were collected during the 90 min after each
infusion. RESULTS: MDMA users reported more positive and fewer negative
emotions and physical symptoms following m-CPP than controls, and were
significantly less likely to report an m-CPP-induced panic attack. Male MDMA
users had diminished cortisol and prolactin responses to m-CPP. CONCLUSIONS:
The present data indicate that MDMA users have alterations in 5-HT neuronal
function, possibly as a consequence of MDMA-induced brain serotonin neural injury
MH - Adult
MH - Affect
MH - drug effects
MH - Anxiety
MH - psychology
MH - Behavior
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Hydrocortisone
MH - blood
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neurosecretory
Systems
MH - Piperazines
MH - diagnostic use
MH - Prolactin
MH - Serotonin
MH - physiology
MH - Serotonin
Agonists
MH - Single-Blind
Method
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 20065490LA
- EngRN - 0 (Hallucinogens)RN - 0 (Piperazines)RN - 0 (Serotonin Agonists)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-23-7
(Hydrocortisone)RN - 50-67-9 (Serotonin)RN - 6640-24-0
(1-(3-chlorophenyl)piperazine)RN - 9002-62-4 (Prolactin)PT - CLINICAL TRIALPT -
JOURNAL ARTICLEID - DA05707/DA/NIDAID - DA05938/DA/NIDAID - DA00206/DA/NIDADA -
20000124IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 200003
UR - PM:0010591869
SO -
Psychopharmacology (Berl) 1999 Nov ;147(1):56-65
44
UI - 48
AU - Morgan JF
TI - Toxic effect of
MDMA on brain serotonin neurons [letter; comment]
MH - Binding Sites
MH - drug effects
MH - Brain
MH - Human
MH - Mental
Disorders
MH - metabolism
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Serotonin
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 99231454LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - COMMENTPT
- LETTERDA - 19990513IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM -
199907RO - M:LC2
UR - PM:0010217102
SO - Lancet 1999 Apr
10 ;353(9160):1268-1269
45
UI - 59
AU - Morgan MJ
AD - Centre for
Substance Abuse Research, Department of Psychology, University of Wales
Swansea, UK. m.j.morgan@swansea.ac.uk
TI - Memory deficits
associated with recreational use of "ecstasy" (MDMA)
AB - Evidence from
both animal, and human, studies suggests that repeated administration of
3,4-methylenedioxymethamphetamine (MDMA: "ecstasy") produces lasting
decreases in serotonergic activity. Serotonin is believed to play a modulatory
role in a variety of psychological processes, including learning and memory.
There are recent reports that polydrug users, who have used ecstasy
recreationally, exhibit selective impairments in memory. However, these studies
did not compare ecstasy users with polydrug users who had not taken ecstasy,
leaving open the possibility that the memory deficits may be associated with a
history of use of other illicit drugs. The present study used the Rivermead
Behavioural Memory test to investigate immediate and delayed recall in: 25
polydrug-users who had taken more than 20 tablets of ecstasy (MDMA group), 22
participants (polydrug controls) who had never taken ecstasy, but, otherwise
has personal characteristics (e.g. age, gender, education, height, weight), and
illicit drug use histories, that were generally not significantly different
from those of the MDMA group, and 19 participants who had not used illicit
drugs but who also had similar personal characteristics (non-drug controls).
Participants in the MDMA group recalled significantly fewer ideas
(approximately 75% of the number of ideas recalled by participants in either of
the other two groups), in both immediate and delayed recall conditions. The two
illicit drug-using groups did differ in their estimated IQ scores and their
duration of use of LSD, but only the latter proved to be a statistically
significant covariate, and the difference in recall performance between the
MDMA and polydrug controls groups remained statistically significant when this
variable was treated as a covariate. The present findings provide the first evidence
that deficits in memory performance in recreational ecstasy users are primarily
associated with past exposure to ecstasy, rather than with the other legal and
illicit drugs consumed by these individuals, and are consistent with reduced
serotonergic modulation of mnemonic function as a result of long-term
neurotoxic effects of MDMA in humans
MH - Adult
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Male
MH - Memory
Disorders
MH - chemically
induced
MH -
Memory,Short-Term
MH - drug effects
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Recall
MH - Serotonin
MH - metabolism
MH - Street Drugs
RP - NOT IN FILE
NT - UI - 99135533LA
- EngRN - 0 (Hallucinogens)RN - 0 (Street Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - JOURNAL
ARTICLEDA - 19990413IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM -
199906
UR - PM:0009952062
SO -
Psychopharmacology (Berl) 1999 Jan ;141(1):30-36
46
UI - 40
AU - Navarro JF
AU - Maldonado E
AD - Area de
Psicobiologia, Facultad de Psicologia, Universidad de Malaga, Spain.
navahuma@uma.es
TI - Behavioral
profile of 3,4-methylenedioxy-methamphetamine (MDMA) in agonistic encounters
between male mice
AB - 1. The effects
of acute administration of 3, 4- methylenedioxymethamphetamine (MDMA), a
synthetic amphetamine derivative (0.5-20 mg/kg, i.p.) on agonistic behavior
elicited by isolation in male mice were examined. 2. Individually housed mice
were exposed to anosmic "standard opponents" 30 min after MDMA
injection, and the encounters were videotaped and evaluated using an
ethologically based analysis. 3. MDMA (5-20 mg/kg) exhibited a behavioral
profile characterized by a reduction of aggression (threat and attack) without
a concomitant increase of immobility, accompanied by a decrease of social
investigation and a increment of exploration from a distance, avoidance/flee
and defense/submission behaviors. 4. This ethopharmacological profile might
suggest an anxiogenic-like activity of MDMA in albino male mice
MH - Aggression
MH - drug effects
MH - Animal
MH - Exploratory
Behavior
MH - Hallucinogens
MH - pharmacology
MH - Male
MH - Mice
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Social Behavior
MH - Social
Dominance
RP - NOT IN FILE
NT - UI - 99297262LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19990817IS -
0278-5846SB - MCY - ENGLANDJC - Q45AA - AuthorEM - 199910
UR - PM:0010368873
SO - Prog Neuropsychopharmacol
Biol Psychiatry 1999 Feb ;23(2):327-334
47
UI - 35
AU - O'Connor A
AU - Cluroe A
AU - Couch R
AU - Galler L
AU - Lawrence J
AU - Synek B
AD - Department of
Critical Care Medicine, Auckland Hospital
TI - Death from
hyponatraemia-induced cerebral oedema associated with MDMA
("Ecstasy") use
MH - Adult
MH - Brain Edema
MH - chemically
induced
MH - Case Report
MH - Fatal Outcome
MH - Female
MH - Hallucinogens
MH - poisoning
MH - Human
MH - Hyponatremia
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Overdose
RP - NOT IN FILE
NT - UI - 99376214LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19990826IS -
0028-8446SB - MCY - NEW ZEALANDJC - OBQEM - 199910
UR - PM:0010448984
SO - N Z Med J 1999
Jul 9 ;112(1091):255-256
48
UI - 20
AU - Pacifici R
AU - Zuccaro P
AU - Farre M
AU - Pichini S
AU - Di Carlo S
AU - Roset PN
AU - Ortuno J
AU - Segura J
AU - de la TR
AD - Clinical
Biochemistry Department, Istituto Superiore di Sanita, Roma, Italy
TI -
Immunomodulating properties of MDMA alone and in combination with alcohol: a
pilot study
AB - Cell-mediated
immune response after the administration of MDMA alone and in combination with
alcohol was evaluated in a randomized, double- blind, double-dummy, cross-over
pilot clinical trial conducted in four healthy MDMA consumers who received
single oral doses of 75 mg MDMA (n = 2) or 100 mg MDMA (n = 2), alcohol (0.8
mg/kg), MDMA and alcohol, or placebo. Acute MDMA treatment produced a
time-dependent immune dysfunction associated with MDMA plasma concentrations.
Although total leukocyte count remained unchanged, there was a decrease in the
CD4 T/CD8 T-cell ratio as well as in the percentage of mature T lymphocytes,
probably because of a decrease in both the percentage and absolute number of T
helper cells. The decrease in CD4 T-cell counts and in the functional
responsiveness of lymphocytes to mitogenic stimulation was dose-dependent. The
correlation between MDMA pharmacokinetics and the profile of MDMA-induced
immune dysfunction suggests that alteration of the immune system may be
mediated by the central nervous system. Alcohol consumption produced a decrease
in T helper cells, B lymphocytes, and PHA-induced lymphocyte proliferation.
Combined MDMA and alcohol produced the greatest suppressive effect on CD4
T-cell count and PHA-stimulated lymphoproliferation. Immune function was
partially restored at 24 hours. These results provide the first evidence that
recreational use of MDMA alone or in combination with alcohol alters the
immunological status
MH -
Adjuvants,Immunologic
MH - blood
MH - pharmacology
MH -
pharmacokinetics
MH -
Administration,Oral
MH - Central Nervous
System Depressants
MH - Cross-Over
Studies
MH - Dose-Response
Relationship,Immunologic
MH - Double-Blind
Method
MH - Drug Synergism
MH - Ethanol
MH - Hallucinogens
MH - Human
MH -
Immunity,Cellular
MH - drug effects
MH - Male
MH - N-Methyl-3,4-
methylenedioxyamphetamine
MH - Pilot Projects
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 20085987LA
- EngRN - 0 (Adjuvants, Immunologic)RN - 0 (Central Nervous System
Depressants)RN - 0 (Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN
- 64-17-5 (Ethanol)PT - CLINICAL TRIALPT - JOURNAL ARTICLEPT - RANDOMIZED
CONTROLLED TRIALDA - 20000119IS - 0024-3205SB - MSB - XCY - ENGLANDJC - L62AA -
AuthorEM - 200003
UR - PM:0010622275
SO - Life Sci
1999 ;65(26):L309-L316
49
UI - 49
AU - Reed LJ
AU - Winstock A
AU - Cleare AJ
AU - McGuire P
TI - Toxic effect of
MDMA on brain serotonin neurons [letter; comment]
MH - Brain
MH - drug effects
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Neurons
MH - metabolism
MH - Sensitivity and
Specificity
MH - Serotonin
MH - Serotonin
Agents
MH -
Substance-Related Disorders
MH -
Tomography,Emission-Computed
RP - NOT IN FILE
NT - UI - 99231453LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - COMMENTPT
- LETTERDA - 19990513IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM -
199907RO - M:LC2
UR - PM:0010217101
SO - Lancet 1999 Apr
10 ;353(9160):1268-1
50
UI - 37
AU - Regenthal R
AU - Kruger M
AU - Rudolph K
AU - Trauer H
AU - Preiss R
TI - Survival after
massive "ecstasy" (MDMA) ingestion [letter]
MH - Adult
MH - Case Report
MH - Hallucinogens
MH - blood
MH - poisoning
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Overdose
MH - diagnosis
RP - NOT IN FILE
NT - UI - 99343333LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - LETTERDA - 19990914IS -
0342-4642SB - MCY - UNITED STATESJC - H2JEM - 199911
UR - PM:0010416925
SO - Intensive Care
Med 1999 Jun ;25(6):640-641
51
UI - 60
AU - Scearce-Levie K
AU - Viswanathan SS
AU - Hen R
AD - Center for
Neurobiology and Behavior, Columbia Unversity, New York, NY 10032, USA
TI - Locomotor
response to MDMA is attenuated in knockout mice lacking the 5- HT1B receptor
AB -
3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive drug of abuse which
is increasingly popular in human recreational drug use. In rats, the drug has
been shown to stimulate locomotion while decreasing exploratory behavior. MDMA
acts as an indirect agonist of serotonin (5- HT) receptors by inducing 5-HT
release by a 5-HT reuptake transporter- dependent mechanism, although it is not
known which 5-HT receptors are important for the behavioral effects of the
drug. In order to examine the role of specific 5-HT receptors, we assessed the
behavioral effects of MDMA on knockout mice lacking the 5-HT1B receptor.
Knockout animals show a reduced locomotor response to MDMA, although delayed
locomotor stimulation is present in these animals. This finding indicates that
the locomotor effects of MDMA are dependent upon the 5-HT1B receptor, at least
in part. In contrast, MDMA eliminates exploratory behavior in both normal and
knockout mice, suggesting that the exploratory suppression induced by MDMA
occurs through mechanisms other than activation of the 5-HT1B receptor. To
confirm these findings, we tested the effects of MDMA on the locomotor and
exploratory behavior of wild- type mice pretreated with GR 127935, a 5-HT1B/1D
receptor antagonist. These mice had an attenuated locomotor response to MDMA,
but still exhibited the drug-induced suppression of exploration
MH - Animal
MH - Exploratory
Behavior
MH - drug effects
MH - physiology
MH - Human
MH - Mice
MH - Mice,Knockout
MH - Motor Activity
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - Rats
MH -
Receptors,Serotonin
MH - deficiency
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 99135510LA
- EngRN - 0 (serotonin 1B receptor)RN - 0 (Receptors, Serotonin)RN - 0
(Serotonin Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT -
JOURNAL ARTICLEID - R01DA09862/DA/NIDADA - 19990413IS - 0033-3158SB - MCY -
GERMANYJC - QGIAA - AuthorEM - 199906
UR - PM:0009952039
SO -
Psychopharmacology (Berl) 1999 Jan ;141(2):154-161
52
UI - 56
AU - Schwab M
AU - Seyringer E
AU - Brauer RB
AU - Hellinger A
AU - Griese EU
TI - Fatal MDMA
intoxication [letter; comment]
MH - Adolescence
MH - Anti-HIV Agents
MH - poisoning
MH - Cytochrome
P-450 CYP2D6
MH - deficiency
MH - genetics
MH - Drug
Interactions
MH - Female
MH - Hallucinogens
MH -
pharmacokinetics
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Ritonavir
RP - NOT IN FILE
NT - UI - 99151469LA
- EngRN - EC 1.14.99.- (Cytochrome P-450 CYP2D6)RN - 0 (Anti-HIV Agents)RN - 0
(Hallucinogens)RN - 0 (Ritonavir)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT
- COMMENTPT - LETTERDA - 19990311IS - 0140-6736SB - ASB - MSB - XCY - ENGLANDJC
- L0SEM - 199905RO - M:LC1
UR - PM:0010029011
SO - Lancet 1999 Feb
13 ;353(9152):593-594
53
UI - 21
AU - Semple DM
AU - Ebmeier KP
AU - Glabus MF
AU - O'Carroll RE
AU - Johnstone EC
AD - University
Department of Psychiatry, Royal Edinburgh Hospital
TI - Reduced in vivo
binding to the serotonin transporter in the cerebral cortex of MDMA ('ecstasy')
users
AB - BACKGROUND: The
use of MDMA ('ecstasy') is common among young people in Western countries.
Animal models of MDMA toxicity suggest a loss of serotonergic neurons, and
potentially implicate in the development of significant psychiatric morbidity
in humans. AIMS: To test whether long- term use of MDMA can produce
abnormalities in cerebral serotonin, but not dopamine, transporter binding
measured by single photon emission computed tomography (SPECT). METHOD: Ten
male regular ecstasy users and 10 well-matched controls recruited from the same
community sources participated in SPECT with the serotonin transporter (SERT)
ligand [123I] beta-CIT. Dopamine transporter binding was determined from scans
acquired 23 hours after injection of the tracer. RESULTS: Ecstasy users showed
a cortical reduction of SERT binding, particularly prominent in primary
sensory-motor cortex, with normal dopamine transporter binding in lenticular
nuclei. CONCLUSIONS: This cross-sectional association study provides suggestive
evidence for specific, at least temporary, serotonergic neurotoxicity of MDMA
in humans
MH - Adolescence
MH - Adult
MH - Carrier
Proteins
MH - drug effects
MH - metabolism
MH - Case-Control
Studies
MH - Cerebral Cortex
MH - Cross-Sectional
Studies
MH - Human
MH - Male
MH - Membrane
Glycoproteins
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Psychomotor
Performance
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
MH -
Tomography,Emission-Computed,Single-Photon
RP - NOT IN FILE
NT - UI - 20087650LA
- EngRN - 0 (serotonin transporter)RN - 0 (Carrier Proteins)RN - 0 (Membrane
Glycoproteins)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 20000124IS -
0007-1250SB - MCY - ENGLANDJC - B1KAA - AuthorEM - 200003
UR - PM:0010621770
SO - Br J Psychiatry
1999 Jul ;175():63-69
54
UI - 24
AU - Shankaran M
AU - Gudelsky GA
AD - College of
Pharmacy, University of Cincinnati, OH 45267-0004, USA
TI - A neurotoxic
regimen of MDMA suppresses behavioral, thermal and neurochemical responses to
subsequent MDMA administration
AB - RATIONALE:
3,4-Methylenedioxymethamphetamine (MDMA) produces a long- term depletion of
serotonin (5-HT) in the rat brain; this depletion may have some functional
consequences. OBJECTIVE: The aim of the present study was to evaluate the acute
effects of MDMA on the extracellular concentrations of dopamine and 5-HT, body
temperature and the 5-HT behavioral syndrome in rats 7 days following a
neurotoxic regimen of MDMA. METHODS: One week after the rats were treated with
a neurotoxic regimen of MDMA (10 mg/kg, i.p., every 2 h for a total of four
injections), the rats were injected with a subsequent injection of MDMA. In
vivo microdialysis combined with HPLC was utilized to measure the extracellular
concentration of 5-HT and dopamine in the striatum. The increase in body
temperature was determined by rectal temperature measurements, and the 5-HT
behavioral syndrome was scored using a rating scale following the
administration of MDMA. RESULTS: The neurotoxic regimen produced a 45%
reduction in brain 5-HT concentrations. The magnitude of the MDMA-induced
increase in the extracellular concentration of 5-HT, but not dopamine, in the
striatum produced by an acute injection of MDMA (7.5 mg/kg, i.p.) was reduced
in rats treated previously with the neurotoxic regimen of MDMA when compared
with that in control animals. In addition, the magnitude of the 5-HT behavioral
syndrome, as well as the hyperthermic response, produced by MDMA was markedly
diminished in rats that had previously received the neurotoxic regimen of MDMA.
CONCLUSIONS: It is concluded that the long-term depletion of brain 5-HT
produced by MDMA is accompanied by impairments in 5-HT function, as evidenced
by the deficits in the neurochemical, thermal and behavioral responses to
subsequent MDMA administration
MH - Animal
MH - Behavior,Animal
MH - drug effects
MH - Body
Temperature
MH - Brain Chemistry
MH - Dopamine
MH - metabolism
MH - Dose-Response
Relationship,Drug
MH - Extracellular
Space
MH - Hallucinogens
MH - administration
& dosage
MH - toxicity
MH -
Injections,Intraperitoneal
MH - Male
MH - Microdialysis
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neurotoxicity
Syndromes
MH - psychology
MH - Neurotoxins
MH - Rats
MH - Rats,Sprague-Dawley
MH - Serotonin
MH - Serotonin
Syndrome
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 20065491LA
- EngRN - 0 (Hallucinogens)RN - 0 (Neurotoxins)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6
(Dopamine)PT - JOURNAL ARTICLEID - DA07427/DA/NIDADA - 20000124IS - 0033-3158SB
- MCY - GERMANYJC - QGIAA - AuthorEM - 200003
UR - PM:0010591870
SO -
Psychopharmacology (Berl) 1999 Nov ;147(1):66-72
55
UI - 8
AU - Virden TB
AU - Baker LE
AD - Department of
Psychology, Western Michigan University, Kalamazoo 49008, USA.
tvirden@imap4.asu.edu
TI - Disruption of
the discriminative stimulus effects of S(+)-3,4- methylenedioxymethamphetamine
(MDMA) by (+/-)-MDMA neurotoxicity: protection by fluoxetine
AB - This study
utilized drug discrimination procedures to assess the functional consequences of
(+/-)-3,4-methylenedioxymethamphetamine (MDMA)-induced serotonin depletion, and
to determine whether concomitant injections of fluoxetine averted these
effects. Twelve male Sprague-Dawley rats were trained to discriminate S(+)-MDMA
(1.5 mg/kg, s.c.) from saline in a two-lever, water-reinforced operant
procedure. After dose generalization tests were completed, training was
suspended, and subjects were administered saline injections twice daily for
four days. Ten days later, tests were conducted with S(+)-MDMA (1.5 mg/kg) and
saline, to ascertain that discriminative stimulus control was maintained in the
absence of training over a two-week period. All subjects received two
additional weeks of training. Subsequently, (+/-)- MDMA (20 mg/kg, s.c.) was
administered twice daily for four days, concomitantly with either 5.0 mg/kg
fluoxetine (FLX) or saline (SAL) injections, and stimulus generalization tests
with S(+)-MDMA and SAL were conducted after ten days. In the rats administered
(+/-)-MDMA + SAL injections, S(+)-MDMA-appropriate responding dropped from
99.24% to 44.99% during S(+)-MDMA generalization tests, and rose from 2.78% to
22.14% during SAL generalization tests. This disruption did not occur, however,
in rats administered the combination of (+/-)-MDMA and FLX injections.
Subsequent training reestablished discriminative stimulus control by S(+)-MDMA
in the (+/-)-MDMA + SAL-treated rats. Postmortem neurochemical assays indicated
that 5-HT levels were significantly reduced in the prefrontal cortices of rats given
(+/-)-MDMA + SAL, compared to both drug-naive control rats and (+/-)-MDMA +
FLX-treated rats. 5-HIAA levels were significantly lower in the prefrontal
cortices of both (+/-)-MDMA + SAL-treated rats and (+/-)-MDMA + FLX-treated
rats, relative to control. These results support previous findings that
fluoxetine protects against (+/-)-MDMA-induced 5-HT depletion. Moreover, this
study demonstrated that drug discrimination is a sensitive assay in which to
examine behavioral correlates of (+/-)-MDMA- induced serotonergic deficits, and
the protection against these deficits by fluoxetine
MH - Animal
MH - Brain Chemistry
MH - drug effects
MH - Discrimination
(Psychology)
MH - Dose-Response
Relationship,Drug
MH - Fluoxetine
MH - therapeutic use
MH - Generalization,Stimulus
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - administration
& dosage
MH - pharmacology
MH - toxicity
MH - Nervous System
Diseases
MH - chemically
induced
MH - pathology
MH - prevention
& control
MH - Rats
MH - Rats,Sprague-Dawley
MH - Serotonin
MH - metabolism
MH - Serotonin
Agents
MH - Serotonin
Uptake Inhibitors
RP - NOT IN FILE
NT - UI - 20241744LA
- EngRN - 0 (Serotonin Agents)RN - 0 (Serotonin Uptake Inhibitors)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN -
54910-89-3 (Fluoxetine)PT - JOURNAL ARTICLEDA - 20000518IS - 0955-8810SB - MCY
- ENGLANDJC - CM8AA - AuthorEM - 200007
UR - PM:0010780832
SO - Behav Pharmacol
1999 Mar ;10(2):195-204
56
UI - 42
AU - Vollenweider FX
AU - Remensberger S
AU - Hell D
AU - Geyer MA
AD - Psychiatric
University Hospital Zurich, Research Department, Switzerland.
vollen@bli.unizh.ch
TI - Opposite
effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in
rats versus healthy humans
AB - RATIONALE:
Prepulse inhibition of acoustic startle refers to the reduction in the startle
response when the startling stimulus is preceded by a weak prepulse stimulus.
This phenomenon provides an operational measure of sensorimotor gating that has
been found to be reduced in patients with schizophrenia and rats treated with
serotonin agonists or serotonin releasers. OBJECTIVE: In this study, we
compared the effects of a serotonin releaser, MDMA, on prepulse inhibition in
laboratory rats and healthy human volunteers. In particular, we investigated
whether MDMA disrupts PPI in humans as observed in animal studies. METHODS:
Rats were tested after placebo and MDMA in a counterbalanced order at an
interval of 1 week, with separate groups of rats being used for each dose of
MDMA (1.7, 5.4 and 17.0 mg/kg). On each test day, rats were first tested after
no injections and retested 2 h later, 10 min after a subcutaneous injection of
placebo or MDMA. For the human study, a placebo-controlled within-subject
design and double-blind procedures were used. Subjects were examined twice at a
2 to 4 week interval after either placebo or drug administration (order being
counterbalanced). On each test day, subjects underwent baseline testing
including psychological and PPI measures. Ninety minutes later, subjects
received placebo or MDMA (1.7 mg/kg PO) and were retested after 75 min during
the peak of behavioral effects of MDMA. RESULTS: As expected, MDMA decreased
prepulse inhibition in a dose-related fashion in rats. In contrast, a typical
recreational dose of MDMA (1.7 mg/kg, orally) increased prepulse inhibition in
subjects experiencing robust psychological effects. CONCLUSIONS: This
surprising disparity between the effects of the drug in rats and humans may
reflect a species- specific difference in the mechanism of action of MDMA or in
the behavioral expression of a similar pharmacological effect, or both
MH - Acoustic
Stimulation
MH - Adult
MH - Affect
MH - drug effects
MH - Analysis of
Variance
MH - Animal
MH - Comparative
Study
MH - Dose-Response
Relationship,Drug
MH - Double-Blind
Method
MH - Habituation
(Psychophysiology)
MH - Human
MH - Middle Age
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - administration
& dosage
MH - pharmacology
MH - Psychometrics
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
Agents
MH - Startle
Reaction
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 99293973LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - CLINICAL TRIALPT - CONTROLLED
CLINICAL TRIALPT - JOURNAL ARTICLEID - DA02925/DA/NIDAID - MH01228/MH/NIMHDA -
19990805IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199910
UR - PM:0010367553
SO -
Psychopharmacology (Berl) 1999 Apr ;143(4):365-372
57
UI - 33
AU - Vollenweider FX
AU - Gamma A
AU - Liechti M
AU - Huber T
TI - Is a single
dose of MDMA harmless? [letter]
MH - Animal
MH - Clinical Trials
MH - standards
MH - Ethics,Medical
MH - Hallucinogens
MH - adverse effects
MH - Human
MH -
Hydroxyindoleacetic Acid
MH - metabolism
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nerve
Degeneration
MH - chemically
induced
MH - Serotonin
RP - NOT IN FILE
NT - UI - 99411458LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 54-16-0
(Hydroxyindoleacetic Acid)PT - LETTERDA - 19991008IS - 0893-133XSB - MCY -
UNITED STATESJC - ADQEM - 199912
UR - PM:0010481844
SO -
Neuropsychopharmacology 1999 Oct ;21(4):598-600
58
UI - 26
AU - Walker TM
AU - Davenport-Jones
JE
AU - Fox RM
AU - Atterwill CK
AD - Department of
Strategic Toxicological Sciences, GlaxoWellcome, Ware, Herts, UK
TI - The neurotoxic
effects of methylenedioxymethamphetamine (MDMA) and its metabolites on rat
brain spheroids in culture
AB - Rat whole-brain
spheroids were used to assess the intrinsic neurotoxicity of
methylenedioxy-methamphetamine (MDMA, Ecstasy) and two of its metabolites,
dihydroxymethamphetamine (DHMA) and 6-hydroxy-MDMA (6-OH MDMA). Exposure of
brain spheroids to MDMA or the metabolite 6-OH MDMA (up to 500 micromol/L) for
5 days in culture did not alter intracellular levels of glutathione (GSH),
glial fibrillary acidic protein (GFAP) or serotonin (5-HT). In contrast,
exposure to the metabolite DHMA, which can deplete intracellular thiols,
significantly increased GSH levels (up to 170% of control) following exposure
to 50 and 100 micromol/L DHMA. There was also a significant reduction in the
levels of glial fibrillary acidic protein (GFAP) and GSH by DHMA at the highest
concentration tested (500 micromol/L) but there was no effect on 5HT. This may
constitute a sublethal neurotoxic compensatory response to DHMA in an attempt
to replenish depleted intraneural GSH levels following metabolite exposure. Rat
whole-brain spheroids may thus be a useful in vitro model to delineate
mechanisms and effects of this class of neurotoxin
MH - Animal
MH - Biological
Markers
MH - Brain
MH - cytology
MH - drug effects
MH - enzymology
MH - metabolism
MH - Brain Diseases
MH - chemically
induced
MH - Cytosol
MH -
Deoxyepinephrine
MH - analogs &
derivatives
MH - toxicity
MH - Dose-Response
Relationship,Drug
MH - Fetus
MH - Glial
Fibrillary Acidic Protein
MH - Glutathione
MH - Lactate
Dehydrogenase
MH - secretion
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH - Serotonin
MH - Serotonin
Agents
MH - Spheroids
MH -
3,4-Methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 20046491LA
- EngRN - EC 1.1.1.27 (Lactate Dehydrogenase)RN - 0 (Biological Markers)RN - 0
(Glial Fibrillary Acidic Protein)RN - 0 (Serotonin Agents)RN - 136706-34-8
(6-hydroxy-N-methyl-3,4-methylenedioxyamphetamine)RN - 15398-87-5
(alpha-methylepinine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN
- 4764-17-4 (3,4-Methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN -
501-15-5 (Deoxyepinephrine)RN - 70-18-8 (Glutathione)PT - JOURNAL ARTICLEDA -
19991229IS - 0742-2091SB - MCY - NETHERLANDSJC - CBTAA - AuthorEM - 200003
UR - PM:0010580546
SO - Cell Biol
Toxicol 1999 Jun ;15(3):137-142
59
UI - 53
AU - Walubo A
AU - Seger D
AD - Division of
Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville,
Tennessee, USA
TI - Fatal
multi-organ failure after suicidal overdose with MDMA, 'ecstasy': case report
and review of the literature
AB - A 53-year-old
prisoner died of multiorgan failure after a suicidal overdose with
3,4-methylenedeoxymethamphetamine (MDMA, 'Ecstasy'). Twelve hours after
ingestion of MDMA, the patient became severely hyperthermic (107.2 degrees F)
with evidence of rhabdomyolysis. He subsequently developed acute respiratory
distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC) and
acute renal failure. At autopsy, plasma concentration of MDMA was 3.05 mg/L.
This case shows that MDMA is still abused in our community and clinicians
should know the symptoms of MDMA intoxication. In particular, MDMA should be
considered when patients have symptoms or signs of increased sympathetic
activity. The pathophysiology and treatment of MDMA-induced hyperthermia are
discussed
MH - Case Report
MH - Disseminated
Intravascular Coagulation
MH - chemically
induced
MH - Fatal Outcome
MH - Fever
MH - Human
MH - Kidney Failure
MH - Male
MH - Middle Age
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - blood
MH - poisoning
MH - Respiratory
Distress Syndrome,Adult
MH - Rhabdomyolysis
MH - Suicide
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 99199798LA
- EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL
ARTICLEDA - 19990621IS - 0960-3271SB - MCY - ENGLANDJC - AQLAA - AuthorEM -
199908
UR - PM:0010100025
SO - Hum Exp Toxicol
1999 Feb ;18(2):119-125
60
UI - 50
AU - Zahn KA
AU - Li RL
AU - Purssell RA
AD - Division of
Emergency Medicine, University of British Columbia, Vancouver, Canada
TI - Cardiovascular
toxicity after ingestion of "herbal ecstacy" [see comments]
AB - "Herbal
Ecstacy" (sic) is an alternative drug of abuse usually containing both
ephedrine and caffeine. Our literature search did not reveal any other reported
cases of cardiovascular toxicity related to herbal "drugs of abuse."
A case of cardiovascular toxicity following the ingestion of herbal ecstacy is
presented. A 21-year-old male presented to the emergency department with an
initial blood pressure of 220/110 mmHg and ventricular dysrhythmias after
ingesting four capsules of herbal ecstacy. He was treated with lidocaine and
sodium nitroprusside, and his symptoms resolved in 9 h. The pathophysiology and
clinical course of ephedrine toxicity are discussed. Emergency physicians
should consider ephedrine preparations in the differential diagnosis of
patients presenting with a sympathomimetic toxidrome. Drugs of abuse containing
"herbal" products can produce serious morbidity and mortality
MH - Adult
MH - Arrhythmia
MH - chemically
induced
MH - Blood Pressure
MH - drug effects
MH - Cardiovascular
System
MH - Case Report
MH - Central Nervous
System Stimulants
MH - adverse effects
MH - Emergencies
MH - Ephedrine
MH - Human
MH - Hypertension
MH - Male
MH - Street Drugs
MH -
Substance-Related Disorders
RP - NOT IN FILE
NT - UI - 99209864LA
- EngRN - 0 (Central Nervous System Stimulants)RN - 0 (Street Drugs)RN -
299-42-3 (Ephedrine)PT - JOURNAL ARTICLEDA - 19990520IS - 0736-4679SB - MCY -
UNITED STATESJC - IBOAA - AuthorEM - 199907RO - M:LC1
UR - PM:0010195489
SO - J Emerg Med
1999 Mar ;17(2):289-291
61
UI - 78
AU - Aguirre N
AU - Ballaz S
AU - Lasheras B
AU - Del Rio J
AD - Department of
Pharmacology, University of Navarra Medical School, Pamplona, Spain
TI - MDMA
('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia:
blockade by drugs preventing 5-hydroxytryptamine depletion
AB - One week after
a single administration of 3,4- methylenedioxymethamphetamine (MDMA HCI, 30
mg/kg i.p.), 5-HT1A receptor density was significantly increased by
approximately 25-30% in the frontal cortex and hypothalamus of rats. The
increased density correlated with the potentiation of the hypothermic response
to the 5- HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-
DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH- DPAT,
were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5
mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA,
prevented the depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also
blocked the effects of this neurotoxin on 5- HT1A receptor density and on
8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT
loss did not correlate, however, with the antagonism of the acute hyperthermic
effect of MDMA. The present results indicate that drugs able to prevent or to
attenuate MDMA-induced 5-HT loss also prevent the changes in 5-HT1A receptor
density as well as the enhanced hypothermic response to the 5-HT1A receptor
agonist 8-OH-DPAT in MDMA-treated rats
MH - Animal
MH - Body
Temperature
MH - drug effects
MH -
Hydroxyindoleacetic Acid
MH - metabolism
MH - Hypothalamus
MH - Hypothermia
MH - chemically
induced
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - antagonists
& inhibitors
MH - pharmacology
MH - Prefrontal
Cortex
MH - Rats
MH - Rats,Wistar
MH -
Receptors,Serotonin
MH - Serotonin
Agents
MH - Serotonin
Agonists
MH - Serotonin
Uptake Inhibitors
MH -
Support,Non-U.S.Gov't
MH - 8-Hydroxy-2-(di-n-propylamino)tetralin
RP - NOT IN FILE
NT - UI - 98314466LA
- EngRN - 0 (Receptors, Serotonin)RN - 0 (Serotonin Agents)RN - 0 (Serotonin
Agonists)RN - 0 (Serotonin Uptake Inhibitors)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 54-16-0 (Hydroxyindoleacetic
Acid)RN - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)PT - JOURNAL
ARTICLEDA - 19980916IS - 0014-2999SB - MCY - NETHERLANDSJC - EN6AA - AuthorEM -
199811
UR - PM:0009652358
SO - Eur J Pharmacol
1998 Apr 10 ;346(2-3):181-188
62
UI - 66
AU - Bango J
AU - Fadon P
AU - Mata F
AU - Rubio G
AU - Santo-Domingo J
AD - Servicio de
Psiquiatria, Hospital Universitario La Paz, Madrid
TI - [Psychiatric
disorders and consumption of ecstasy drug (MDMA): review of published case reports]
AB - BACKGROUND:
Ecstasy use have raised in recent years and it have been related to
psychopathological symptoms. The comsumption pattern associated with
psychiatric complications is unknown. METHOD: Thirty- six case reports about
psychiatric complications due to ecstasy and published from 1985 to 1997 were
studied. RESULTS: The disorders with higher prevalence were psychosis (n = 21),
panic attacks (n = 12) and depressive symptoms (n = 3). Seventy two per cent
were substance abusers. Urinary drugs screening were present in 28%, only in
two subjects might detect amphetamine. Men had higher MDMA doses compsumption
and higher prevalence of background psychiatric disorders than women. Subjects
with psychotic symptomatology had more psychiatric background, higher doses of
MDMA comsumption and for a long time than individuals with depressive or panic
attacks symptomatology. CONCLUSIONS: The review of the case reports of
psychiatric complications related to ecstasy use do not allow to conclude that
ecstasy use was the main responsible factor for psychiatric symptoms. They
could be related to an individual vulnerability and or to lasting of
comsumption
MH - Adolescence
MH - Adult
MH - English
Abstract
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Male
MH - Mental
Disorders
MH - chemically
induced
MH - psychology
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Retrospective
Studies
MH -
Substance-Related Disorders
RP - NOT IN FILE
NT - UI - 99024992LA
- SpaRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEPT - REVIEWPT -
REVIEW LITERATUREDA - 19990225IS - 0300-5062CY - SPAINJC - 2AMAA - AuthorEM -
199904
UR - PM:0009807860
SO - Actas Luso Esp
Neurol Psiquiatr Cienc Afines 1998 Jul ;26(4):260-263
63
UI - 96
AU - Bilsky EJ
AU - Montegut MJ
AU - Nichols ML
AU - Reid LD
AD - Department of
Biological Sciences, University of Northern Colorado, Greeley 80639, USA.
ejbilsk@bentley.univnorthco.edu
TI - CGS 10746B, a
novel dopamine release inhibitor, blocks the establishment of cocaine and MDMA
conditioned place preferences
AB - Cocaine and
methylenedioxymethamphetamine (MDMA), two drugs self- administered by humans
and laboratory animals, have previously been shown to produce conditioned place
preferences (CPPs) among rats, an index of drug-reward relevant events. Both of
these agents increase functional levels of dopamine that may be critical to
their rewarding properties. Here, the effects of doses of CGS 10746B, an agent
reported to attenuate the release of dopamine without occupying dopamine
receptors, are assessed on cocaine and MDMA's ability to produce a CPP. CGS
10746B dose dependently blocked the establishment of a MDMA CPP. A 30 mg/kg
dose of CGS 10746B, which completely blocked the MDMA CPP, also blocked the
establishment of a cocaine CPP. Release of dopamine appears critical to the
ability of these agents to establish a CPP
MH - Analysis of
Variance
MH - Animal
MH - Choice Behavior
MH - drug effects
MH - Cocaine
MH - antagonists
& inhibitors
MH -
Conditioning,Operant
MH - Cues
MH - Dopamine
MH - metabolism
MH - Dopamine Agents
MH - pharmacology
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Support,U.S.Gov't,P.H.S.
MH - Thiazepines
RP - NOT IN FILE
NT - UI - 98103795LA
- EngRN - 0 (Dopamine Agents)RN - 0 (Thiazepines)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-36-2 (Cocaine)RN - 51-61-6
(Dopamine)RN - 81382-52-7 (CGS 10746B)PT - JOURNAL ARTICLEID - DA
04440/DA/NIDAID - DA 08937/DA/NIDADA - 19980309IS - 0091-3057SB - MCY - UNITED
STATESJC - P3QAA - AuthorEM - 199805
UR - PM:0009443558
SO - Pharmacol
Biochem Behav 1998 Jan ;59(1):215-220
64
UI - 62
AU - Bolla KI
AU - McCann UD
AU - Ricaurte GA
AD - Department of
Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
TI - Memory
impairment in abstinent MDMA ("Ecstasy") users [see comments]
AB - BACKGROUND:
Methylenedioxymethamphetamine (MDMA, or "Ecstasy") is a popular
recreational drug of abuse that is known to damage brain serotonergic neurons
in animals and possibly humans. Few functional consequences of MDMA-induced
serotonin (5-HT) neurotoxicity have been identified, either in animals or
humans. This study sought to determine whether individuals with a history of
extensive MDMA use showed evidence of memory impairment, because brain
serotonin has been implicated in mnemonic function. METHOD: The authors
compared 24 abstinent MDMA users and 24 control subjects on several
standardized tests of memory, after matching subjects for age, gender,
educational level, and vocabulary score (a surrogate of verbal intelligence).
The authors also explored correlations between changes in memory function and
decrements in CSF 5-hydroxyindoleacetic acid (5-HIAA), which serves as a marker
of central 5-HT neural function. RESULTS: Greater use of MDMA (total milligrams
per month) was associated with greater impairment in immediate verbal memory (p
< 0.02) and delayed visual memory (p < 0.06). Furthermore, lower
vocabulary scores were associated with stronger dose-related effects, with men
having greater dose- related deficits than women. Lastly, lower concentrations
of CSF 5-HIAA were associated with poorer memory performance. CONCLUSION:
Abstinent MDMA users have impairment in verbal and visual memory. The extent of
memory impairment correlates with the degree of MDMA exposure and the reduction
in brain 5-HT, as indexed by CSF 5-HIAA
MH - Adult
MH - Female
MH - Human
MH -
Hydroxyindoleacetic Acid
MH - cerebrospinal
fluid
MH - Male
MH - Memory
MH - drug effects
MH - Middle Age
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - administration
& dosage
MH - toxicity
MH - Pattern
Recognition,Visual
MH - Regression
Analysis
MH - Serotonin
MH - Serotonin
Agents
MH - Street Drugs
MH -
Support,U.S.Gov't,P.H.S.
MH - Verbal Learning
RP - NOT IN FILE
NT - UI - 99071140LA
- EngRN - 0 (Serotonin Agents)RN - 0 (Street Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 54-16-0
(Hydroxyindoleacetic Acid)PT - JOURNAL ARTICLEID - R01 DA06275/DA/NIDAID -
DA05707/DA/NIDAID - DA05938/DA/NIDAID - +DA - 19981230IS - 0028-3878SB - ASB -
MCY - UNITED STATESJC - NZ0AA - AuthorEM - 199903
UR - PM:0009855498
SO - Neurology 1998
Dec ;51(6):1532-1537
65
UI - 84
AU - Brody S
AU - Krause C
AU - Veit R
AU - Rau H
AD - Institute of
Medical Psychology and Behavioral Neurobiology, Eberhard- Karls University of
Tubingen, Germany. stuart.brody@uni-tuebingen.de
TI - Cardiovascular
autonomic dysregulation in users of MDMA ("Ecstasy")
AB - The present
study examined resting heart rate variability (HRV; an index of parasympathetic
tone) and heart rate response to the Valsalva maneuver (Valsalva ratio; an
index of overall autonomic responsiveness) in 12 repeat users of
3.4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and a matched
comparison group of presumed nonusers. HRV and Valsalva ratio were smaller in
users than in controls. Three out of 12 MDMA users but no controls had Valsalva
ratios below 1.50, the cut- off for autonomic dysfunction. In several users,
there was a total absence of post-Valsalva release bradycardia. All MDMA users
were polydrug users. Parasympathetic cardiovascular tone appears impaired in
repeat MDMA users, although the ubiquitous problems in such epidemiologic
designs (including lack of testing before the first use of the drug and
confounding with use of other drugs) preclude definitive causal interpretations
MH - Adolescence
MH - Adult
MH - Autonomic
Nervous System
MH - drug effects
MH - Blood Pressure
MH - Comparative
Study
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Heart Rate
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 98261212LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT
- JOURNAL ARTICLEDA - 19980807IS - 0033-3158SB - MCY - GERMANYJC - QGIAA -
AuthorEM - 199810
UR - PM:0009600585
SO -
Psychopharmacology (Berl) 1998 Apr ;136(4):390-393
66
UI - 79
AU - Colado MI
AU - Granados R
AU - O'Shea E
AU - Esteban B
AU - Green AR
AD - Departamento de
Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
TI - Role of
hyperthermia in the protective action of clomethiazole against MDMA
('ecstasy')-induced neurodegeneration, comparison with the novel NMDA channel
blocker AR-R15896AR
AB - 1. The
immediate effect of administration of 3,4- methylenedioxymethamphetamine (MDMA
or 'ecstasy') on rectal temperature and the effect of putative neuroprotective
agents on this change has been examined in rats. The influence of the
temperature changes on the long term MDMA-induced neurodegeneration of cerebral
5- hydroxytryptamine (5-HT) nerve terminals was also examined. 2. The novel low
affinity N-methyl-D-aspartate (NMDA) receptor channel blocker AR-R15896AR (20
mg kg(-1), i.p.) given 5 min before and 55 min after MDMA (15 mg kg(-1), i.p.)
did not prevent the MDMA-induced hyperthermia and did not alter either the
MDMA-induced neurodegenerative loss of 5- HT and 5-hydroxyindoleacetic acid
(5-HIAA) in cortex, striatum and hippocampus or loss of [3H]-paroxetine binding
in cortex 7 days later. 3. The neuroprotective agent clomethiazole (50 mg
kg(-1), i.p.) given 5 min before and 55 min after MDMA (15 mg kg(-1)) abolished
the MDMA- induced hyperthermic response and markedly attenuated the loss of
5-HT, 5-HIAA and [3H]-paroxetine binding in the brain regions examined 7 days
later. 4. When rats treated with MDMA plus clomethiazole were kept at high
ambient temperature for 5 h post-MDMA, thereby keeping their body temperature
elevated to near that seen in rats given MDMA alone, the MDMA-induced loss of
5-HT, 5-HIAA and [3H]-paroxetine was still attenuated. However, the protection
(39%) afforded by the clomethiazole administration was less than seen in rats
kept at normal ambient temperature (75%). 5. These data support the proposals
of others that NMDA receptor antagonists are neuroprotective against
MDMA-induced degeneration only if they induce hypothermia and further suggest
that increased glutamate activity may not be involved in the neurotoxic action
of MDMA. 6. These data further demonstrate that a proportion of the
neuroprotective action of clomethiazole is due to an effect on body temperature
but that, in addition, the compound protects against MDMA- induced damage by an
unrelated mechanism
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - physiology
MH - Brain Chemistry
MH - Chlormethiazole
MH - pharmacology
MH - Comparative
Study
MH - Excitatory
Amino Acid Antagonists
MH - Fever
MH - physiopathology
MH -
Hydroxyindoleacetic Acid
MH - metabolism
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - antagonists
& inhibitors
MH - toxicity
MH - Nerve
Degeneration
MH - chemically
induced
MH - prevention
& control
MH - Neuroprotective
Agents
MH - Paroxetine
MH -
pharmacokinetics
MH - Pyridines
MH - Rats
MH -
Receptors,N-Methyl-D-Aspartate
MH - Serotonin
MH - Serotonin
Uptake Inhibitors
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 98309686LA
- EngRN - 0 (Excitatory Amino Acid Antagonists)RN - 0 (FPL 15896AR)RN - 0
(Neuroprotective Agents)RN - 0 (Pyridines)RN - 0 (Receptors,
N-Methyl-D-Aspartate)RN - 0 (Serotonin Uptake Inhibitors)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 533-45-9
(Chlormethiazole)RN - 54-16-0 (Hydroxyindoleacetic Acid)RN - 61869-08-7
(Paroxetine)PT - JOURNAL ARTICLEDA - 19980916IS - 0007-1188SB - MCY - ENGLANDJC
- B00AA - AuthorEM - 199811
UR - PM:0009647471
SO - Br J Pharmacol
1998 Jun ;124(3):479-484
67
UI - 92
AU - Connor TJ
AU - McNamara MG
AU - Finn D
AU - Currid A
AU - O'Malley M
AU - Redmond AM
AU - Kelly JP
AU - Leonard BE
AD - Department of
Pharmacology, University College Galway, Ireland
TI - Acute
3,4-methylenedioxymethamphetamine(MDMA) administration produces a rapid and
sustained suppression of immune function in the rat
AB -
(+)-3,4-Methylenedioxymethamphetamine (MDMA;'Ecstasy') is a ring substituted
phenylisopropylamine that is structurally related to both amphetamines and
hallucinogens. The unique behavioural activating properties of MDMA have led to
its widespread abuse. MDMA induces many neurochemical, behavioural and
endocrine alterations which closely resemble those elicited by exposure to
acute stress, suggesting that MDMA could be regarded as a 'chemical stressor'.
In addition to the neurochemical, behavioural and endocrine effects of stressor
exposure, it has been reported that stress produces alterations in immune
function. However, to date the effects of MDMA on immune function have been
restricted to in vitro investigations. In this study we report, for the first
time, that acute in vivo administration of MDMA (20 mg/kg, i.p.) produced a
rapid (within 30 min) suppression of Con A- induced lymphocyte proliferation
and a profound reduction in the total leucocyte count in rats that persisted
for at least 6 h following injection. These alterations in immune function were
accompanied by a significant increase in plasma corticosterone concentrations
30 min post MDMA administration which had returned to baseline values within 6
h of drug administration. In addition, there was a significant depletion in
cortical 5-HT concentrations both 30 min and 6 h after MDMA administration. The
results of this study provide evidence that in addition to the well established
toxic effects of MDMA on the central serotonergic system, a single
administration of this widely abused drug induces a rapid and sustained
suppression of immune function
MH - Animal
MH - Cerebral Cortex
MH - drug effects
MH - metabolism
MH - Concanavalin A
MH - Corticosterone
MH - blood
MH - Female
MH - Hallucinogens
MH - administration
& dosage
MH - toxicity
MH -
Hydroxyindoleacetic Acid
MH - analysis
MH -
Immunity,Cellular
MH - Leukocyte Count
MH - Lymphocyte
Transformation
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH - Serotonin
Agents
MH - T-Lymphocytes
MH - immunology
MH - Time Factors
RP - NOT IN FILE
NT - UI - 98165670LA
- EngRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 11028-71-0
(Concanavalin A)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
50-22-6 (Corticosterone)RN - 50-67-9 (Serotonin)RN - 54-16-0 (Hydroxyindoleacetic
Acid)PT - JOURNAL ARTICLEDA - 19980511IS - 0162-3109SB - MCY - NETHERLANDSJC -
GY3AA - AuthorEM - 199807
UR - PM:0009506825
SO -
Immunopharmacology 1998 Jan ;38(3):253-260
68
UI - 76
AU - Dafters RI
AU - Lynch E
AD - Psychology
Department, Glasgow University, UK
TI - Persistent loss
of thermoregulation in the rat induced by 3,4- methylenedioxymethamphetamine
(MDMA or "Ecstasy") but not by fenfluramine
AB - Using
radio-biotelemetry, the timecourse of recovery and sensitivity to ambient
temperature (Ta) of the thermogenic response of methylenedioxymethamphetamine
(MDMA or "Ecstasy") was examined. Ambient temperatures of 17 and 22
degrees C produced very different response profiles, with the lower temperature
producing a hypothermic response to 10 and 15 mg/kg doses of MDMA, and the
higher temperature producing a profound hyperthermia to the same doses.
Although the peak responses to the drug had subsided within 5 h of
administration, residual effects, in the form of an elevation of body
temperature during the "low" phase of the diurnal cycle, were present
for a further 48 h. Long- lasting disruption of the thermoregulatory system
following a short series of MDMA administrations (10 mg/kg once per day for 4
days) was shown by exposing the rats in the undrugged state to a
thermoregulatory challenge, consisting of 60-min exposure to a Ta of 30 degrees
C, at 1 week before, and at 4 weeks and 14 weeks after the drug administration.
MDMA-treated rats showed a prolonged hyperthermic response to the challenge at
both post-drug intervals compared with fenfluramine- treated rats and
saline-treated controls. Thus, the results indicate both that MDMA's
thermogenic effects are more sensitive to Ta than previously demonstrated, and
that the serotonergic neurotoxicity of the drug may produce long-lasting
changes in thermoregulatory mechanisms
MH - Amphetamine
MH - pharmacology
MH - Animal
MH - Body
Temperature Regulation
MH - drug effects
MH - Dopamine Agents
MH - Female
MH - Fenfluramine
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH - Rats,Wistar
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 98382417LA
- EngRN - 0 (Dopamine Agents)RN - 0 (Serotonin Agents)RN - 300-62-9
(Amphetamine)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
458-24-2 (Fenfluramine)PT - JOURNAL ARTICLEDA - 19981026IS - 0033-3158SB - MCY
- GERMANYJC - QGIAA - AuthorEM - 199901
UR - PM:0009718291
SO - Psychopharmacology
(Berl) 1998 Jul ;138(2):207-212
69
UI - 77
AU - Frederick DL
AU - Ali SF
AU - Gillam MP
AU - Gossett J
AU - Slikker W
AU - Paule MG
AD - Division of
Neurotoxicology, National Center for Toxicological Research, Jefferson Arkansas
72079, USA. df50029@GlaxoWellcome.com
TI - Acute effects
of dexfenfluramine (d-FEN) and methylenedioxymethamphetamine (MDMA) before and
after short-course, high-dose treatment
AB - The acute
behavioral effects of methylenedioxymethamphetamine (MDMA) and dexfenfluramine
(d-FEN) were assessed in six rhesus monkeys using performance in the National
Center for Toxicological Research (NCTR) Operant Test Battery (OTB); three
additional animals served as controls for neurochemical endpoints. The OTB
consists of five food-reinforced tasks designed to model aspects of learning,
short-term memory and attention, time estimation, motivation, and color and
position discrimination. Shortly after the acute effects of each drug were
determined, three of the monkeys received a short-course, high-dose exposure
(2x /day x 4 days, intramuscular (i.m.) injections) of MDMA (10 mg/kg), while
three monkeys were exposed to an identical regimen of d-FEN (5 mg/kg).
Approximately one month later, the acute effects of each drug were again determined.
In monkeys exposed to high-dose d-FEN, the sensitivities of the OTB tasks to
acute disruption by either MDMA or d-FEN were essentially unchanged.
Conversely, monkeys treated with high-dose MDMA were less sensitive to the
acute behavioral effects of both drugs, although such an effect was seen more
frequently for d-FEN and was OTB task specific. Thus a residual behavioral
tolerance to the acute behavioral effects of MDMA and d-FEN was noted after
high-dose MDMA exposure, but not after high-dose d-FEN exposure. These findings
are surprising, as similar neurochemical effects (i.e., significant decreases
of ca. 50% in serotonin in frontal cortex and hippocampus) were observed in all
monkeys approximately six months after short- course, high-dose MDMA or d-FEN
treatment
MH - Animal
MH - Behavior,Animal
MH - drug effects
MH - Brain
MH - metabolism
MH - Dose-Response
Relationship,Drug
MH - Drug
Administration Schedule
MH - Drug Tolerance
MH - Fenfluramine
MH - administration
& dosage
MH - pharmacology
MH - Macaca mulatta
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Neuropsychological Tests
MH - Serotonin
MH - Time Factors
RP - NOT IN FILE
NT - UI - 98333273LA
- EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 458-24-2
(Fenfluramine)RN - 50-67-9 (Serotonin)PT - JOURNAL ARTICLEDA - 19980813IS -
0077-8923SB - MSB - XCY - UNITED STATESJC - 5NMAA - AuthorEM - 199810
UR - PM:0009668676
SO - Ann N Y Acad
Sci 1998 May 30 ;844():183-190
70
UI - 61
AU - Greer GR
AU - Tolbert R
AD - Heffter
Research Institute, Santa Fe, New Mexico, USA
TI - A method of
conducting therapeutic sessions with MDMA
AB - A method for
preparing clients and conducting therapeutic sessions with
3,4-methylenedioxymethamphetamine (MDMA) is described, with emphasis on the
need for careful attention to the mental set of therapists and clients and the
setting of the session. The therapists' belief was that MDMA inhibited the fear
response to a perceived emotional threat, allowing the client to place the
emotional sequelae of past experiences into a more realistic perspective in
their current emotional lives and relationships. Clients were carefully
screened and prepared until they had a clear purpose for the session, including
a willingness to experience and to learn from anything that might happen.
Sympathomimetic effects of MDMA determined the medical contraindications, and
clients with histories of serious functional psychiatric impairments were
excluded. Total doses of 75-150 mg, plus 50 mg if requested later, were
administered, followed by clients lying down and listening to music with
eyeshades and headphones during the peak MDMA effect. Screening and follow-up
questionnaires were utilized. Two case histories are presented: a man achieving
relief of pain from multiple myeloma, and a woman finding relief from problems
as the daughter of Holocaust survivors. Use of consciousness-altering drugs in
other contexts is discussed
MH - Adult
MH - Aged
MH - Bone Neoplasms
MH - complications
MH - Case Report
MH - Depressive
Disorder
MH - drug therapy
MH - psychology
MH - Female
MH - Hallucinogens
MH - therapeutic use
MH - Human
MH - Male
MH - Multiple
Myeloma
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Pain,Intractable
MH - therapy
MH - Psychotherapy
MH - methods
RP - NOT IN FILE
NT - UI - 99122231LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19990329IS -
0279-1072SB - MCY - UNITED STATESJC - JLPAA - AuthorEM - 199906
UR - PM:0009924843
SO - J Psychoactive
Drugs 1998 Oct ;30(4):371-379
71
UI - 63
AU - Henry JA
AU - Hill IR
TI - Fatal
interaction between ritonavir and MDMA [letter] [see comments]
MH - Acquired
Immunodeficiency Syndrome
MH - drug therapy
MH - Adult
MH - Anti-HIV Agents
MH - poisoning
MH - Case Report
MH - Drug
Interactions
MH - Drug
Therapy,Combination
MH - Fatal Outcome
MH - Hallucinogens
MH - Heart Arrest
MH - chemically
induced
MH - Human
MH - Liver
Diseases,Alcoholic
MH - complications
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Ritonavir
RP - NOT IN FILE
NT - UI - 99063100LA
- EngRN - 0 (Anti-HIV Agents)RN - 0 (Hallucinogens)RN - 0 (Ritonavir)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - LETTERDA - 19981222IS -
0140-6736SB - ASB - MSB - XCY - ENGLANDJC - L0SEM - 199902RO - M:LC1
UR - PM:0009848354
SO - Lancet 1998 Nov
28 ;352(9142):1751-1752
72
UI - 80
AU - Henry JA
AU - Fallon JK
AU - Kicman AT
AU - Hutt AJ
AU - Cowan DA
AU - Forsling M
TI - Low-dose MDMA
("ecstasy") induces vasopressin secretion [letter]
MH - Adult
MH - Argipressin
MH - blood
MH - secretion
MH - Comparative
Study
MH - Hallucinogens
MH - pharmacology
MH - Human
MH - Hyponatremia
MH - chemically
induced
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 98297877LA
- EngRN - 0 (Hallucinogens)RN - 113-79-1 (Argipressin)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - CLINICAL TRIALPT - CONTROLLED
CLINICAL TRIALPT - LETTERDA - 19980710IS - 0140-6736SB - ASB - MSB - XCY -
ENGLANDJC - L0SEM - 199809
UR - PM:0009635954
SO - Lancet 1998 Jun
13 ;351(9118):1784
73
UI - 89
AU - Kalivas PW
AU - Duffy P
AU - White SR
AD - Alcohol and
Drug Abuse Program, Washington State University, Pullman 99164-6520, USA
TI - MDMA elicits
behavioral and neurochemical sensitization in rats
AB - Rats were
treated with repeated injections of saline or one of two doses of
(+/-)3,4-methylenedioxymethamphetamine (MDMA; 5 or 20 mg/kg, s.c.). Rats
pretreated with either of the two repeated MDMA treatment regimens demonstrated
an augmented increase in motor activity to an injection of MDMA made 12 days
after the last repeated injection compared with either the first MDMA injection
or MDMA given to animals pretreated with repeated saline. Furthermore, animals
pretreated with the highest dose of repeated MDMA revealed a greater behavioral
response to cocaine (15 mg/kg, i.p.). Microdialysis was conducted in the
nucleus accumbens and the capacity of MDMA (5 mg/kg, s.c.) to elevate
extracellular dopamine content was augmented in rats pretreated with repeated
MDMA compared with the animals pretreated with repeated saline. These data
reveal repeated MDMA administration produces behavioral sensitization and
enhanced dopamine transmission in the nucleus accumbens of rats
MH - Animal
MH - Behavior,Animal
MH - drug effects
MH - Biogenic
Monoamines
MH - metabolism
MH - Brain Chemistry
MH -
Chromatography,High Pressure Liquid
MH - Cocaine
MH - pharmacology
MH - Dopamine
MH - Dopamine Uptake
Inhibitors
MH -
Electrochemistry
MH - Hallucinogens
MH - Male
MH - Microdialysis
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nucleus
Accumbens
MH - Rats
MH -
Rats,Sprague-Dawley
MH -
Support,U.S.Gov't,P.H.S.
MH - Time Factors
RP - NOT IN FILE
NT - UI - 98233146LA
- EngRN - 0 (Biogenic Monoamines)RN - 0 (Dopamine Uptake Inhibitors)RN - 0
(Hallucinogens)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
50-36-2 (Cocaine)RN - 51-61-6 (Dopamine)PT - JOURNAL ARTICLEID -
DA-08116/DA/NIDAID - DA-03906/DA/NIDAID - MH-40817/MH/NIMHID - +DA - 19980623IS
- 0893-133XSB - MCY - UNITED STATESJC - ADQAA - AuthorEM - 199808
UR - PM:0009571655
SO -
Neuropsychopharmacology 1998 Jun ;18(6):469-479
74
UI - 73
AU - Kramer HK
AU - Poblete JC
AU - Azmitia EC
AD - Department of
Psychiatry, New York University Medical Center, Millhauser Labs, New York
10016, USA
TI -
Characterization of the translocation of protein kinase C (PKC) by 3,4-
methylenedioxymethamphetamine (MDMA/ecstasy) in synaptosomes: evidence for a
presynaptic localization involving the serotonin transporter (SERT)
AB - 3,
4-methylenedioxymethamphetamine (MDMA or Ecstasy) is a substituted amphetamine
whose acute and long-term effects on the serotonin system are dependent on an
interaction with the 5-HT uptake transporter (SERT). Although much of the work
dedicated to the study of this compound has focused on its ability to release
monoamines, this drug has many important metabolic consequences on neurons and
glial cells. The identification of these physiological responses will help to
bridge the gap that exists in the information between the acute and neurotoxic
effects of amphetamines. Substituted amphetamines have the ability to produce a
long-term translocation of protein kinase C (PKC) in vivo, and this action may
be crucial to the development of serotonergic neurotoxicity. Our earlier
results suggested that PKC activation occurred through pre- and postsynaptic
mechanisms. Because the primary site of action of these drugs is the 5-HT
transporter, we now expand on our previous results and attempt to characterize
MDMA's ability to translocate PKC within cortical 5-HT nerve terminals. In
synaptosomes, MDMA produced a concentration-dependent increase in
membrane-bound PKC (as measured by 3H-phorbol 12, 13 dibutyrate, 3H-PDBu)
bindings sites. This response was abolished by cotreatment with the specific serotonin
reuptake inhibitor (SSRI), fluoxetine, but not by the 5-HT2A/2C antagonist,
ketanserin. In contrast, full agonists to 5-HT1A and 5-HT2 receptors did not
produce significant PKC translocation. MDMA-mediated PKC translocation also
requires the presence of extracellular calcium ions. Using assay conditions
where extracellular calcium was absent prevented in vitro activation of PKC by
MDMA. Prolonged PKC translocation has been hypothesized to contribute to the
calcium- dependent neurotoxicity produced by substituted amphetamines. In
addition, many physiological processes within 5-HT nerve terminals, including
5-HT reuptake and vesicular serotonin release, are susceptible to modification
by PKC-dependent protein phosphorylation. Our results suggest that prolonged
activation of PKC within the 5-HT nerve terminal may contribute to lasting
changes in the homeostatic function of 5-HT neurons, leading to the
degeneration of specific cellular elements after repeated MDMA exposure
MH -
p-Chloroamphetamine
MH - pharmacology
MH - Animal
MH - Calcium
MH - Cerebral Cortex
MH - drug effects
MH - metabolism
MH - Comparative
Study
MH - Female
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Protein Kinase
C
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
Agents
MH - Synaptosomes
RP - NOT IN FILE
NT - UI - 98384702LA
- EngRN - EC 2.7.1.- (Protein Kinase C)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 64-12-0 (p-Chloroamphetamine)RN -
7440-70-2 (Calcium)PT - JOURNAL ARTICLEDA - 19981125IS - 0893-133XSB - MCY -
UNITED STATESJC - ADQAA - AuthorEM - 199901
UR - PM:0009718590
SO -
Neuropsychopharmacology 1998 Oct ;19(4):265-277
75
UI - 81
AU - Malberg JE
AU - Seiden LS
AD - University of
Chicago, Department of Pharmacological and Physiological Sciences, Chicago,
Illinois 60637, USA
TI - Small changes
in ambient temperature cause large changes in 3,4-
methylenedioxymethamphetamine (MDMA)-induced serotonin neurotoxicity and core
body temperature in the rat
AB - The amphetamine
derivative 3,4-methylenedioxymethamphetamine (MDMA) is a drug of abuse and has
been shown to be neurotoxic to 5-HT terminals in many species. MDMA-engendered
neurotoxicity has been shown to be affected by both ambient temperature and core
body temperature. We now report that small (2 degreesC) changes in ambient
temperature produce changes in core temperature in MDMA-treated rats, but the
same changes in ambient temperature do not affect core temperature of
saline-treated animals. Furthermore, increases in core temperature of
MDMA-treated animals increase neurotoxicity. Rats were given MDMA (20 or 40
mg/kg) or saline and placed in an ambient temperature of 20, 22, 24, 26, 28, or
30 degreesC using a novel temperature measurement apparatus that controls
ambient temperature +/-0.5 degrees C. Two weeks after MDMA treatment, the rats
were killed, and regional 5-HT and 5-hydroxyindole acetic acid levels were
analyzed as a measure of neurotoxicity. Rats treated with MDMA at 20 and 22
degrees C showed a hypothermic core temperature response. Treatment with MDMA
at 28 and 30 degreesC produced a hyperthermic response. At ambient temperatures
of 20-24 degrees C, neurotoxicity was not observed in the frontal cortex,
somatosensory cortex, hippocampus, or striatum. At ambient temperatures of
26-30 degrees C, neurotoxicity was seen and correlated with core temperature in
all regions examined. These data indicate that ambient temperature has a
significant affect on MDMA neurotoxicity, core temperature, and
thermoregulation in rats. This finding has implications on both the temperature
dependence of the mechanism of MDMA neurotoxicity and human use because fatal
hyperthermia is associated with MDMA use in humans
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - Body
Temperature Regulation
MH - Brain Chemistry
MH - Corpus Striatum
MH - chemistry
MH - Dopamine
MH - analysis
MH - Fever
MH - metabolism
MH - mortality
MH - Frontal Lobe
MH - Hippocampus
MH - Homovanillic
Acid
MH - Hydroxyindoleacetic
Acid
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Neurotoxins
MH - pharmacology
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH - Serotonin
Agents
MH - Sodium Chloride
MH - Somatosensory
Cortex
MH -
Support,U.S.Gov't,P.H.S.
MH - Temperature
MH -
3,4-Dihydroxyphenylacetic Acid
RP - NOT IN FILE
NT - UI - 98299899LA
- EngRN - 0 (Neurotoxins)RN - 0 (Serotonin Agents)RN - 102-32-9
(3,4-Dihydroxyphenylacetic Acid)RN - 306-08-1 (Homovanillic Acid)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN -
51-61-6 (Dopamine)RN - 54-16-0 (Hydroxyindoleacetic Acid)RN - 7647-14-5 (Sodium
Chloride)PT - JOURNAL ARTICLEID - DA00085/DA/NIDAID - MH-105-62/MH/NIMHDA -
19980702IS - 0270-6474SB - MCY - UNITED STATESJC - JDFAA - AuthorEM - 199809
UR - PM:0009634574
SO - J Neurosci 1998
Jul 1 ;18(13):5086-5094
76
UI - 65
AU - McCann UD
AU - Szabo Z
AU - Scheffel U
AU - Dannals RF
AU - Ricaurte GA
AD - Biological
Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland, USA
TI - Positron
emission tomographic evidence of toxic effect of MDMA ("Ecstasy") on
brain serotonin neurons in human beings [see comments]
AB - BACKGROUND:
(+/-)3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular
recreational drug that selectively damages brain serotonin (5- HT) neurons in
animals at doses that closely approach those used by humans. We investigated
the status of brain 5-HT neurons in MDMA users. METHODS: We enrolled 14
previous users of MDMA who were currently abstaining from use and 15 controls
who had never used MDMA. We used positron emission tomography (PET) with the
radioligand carbon-11- labelled McN-5652, which selectively labels the 5-HT
transporter. We analysed whether there were differences in 5-HT transporter
binding between abstinent MDMA users and participants in the control group.
Blood and urine samples were taken and tested to check for abstinence.
FINDINGS: MDMA users showed decreased global and regional brain 5-HT
transporter binding compared with controls. Decreases in 5-HT transporter
binding positively correlated with the extent of previous MDMA use.
INTERPRETATION: Quantitative PET studies with a ligand selective for 5-HT
transporters can be used to assess the status of 5- HT neurons in the living
human brain. We show direct evidence of a decrease in a structural component of
brain 5-HT neurons in human MDMA users
MH - Adult
MH - Brain
MH - drug effects
MH - Comparative
Study
MH - Female
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Neurons
MH - metabolism
MH - Serotonin
MH - Serotonin
Agents
MH -
Support,U.S.Gov't,P.H.S.
MH -
Tomography,Emission-Computed
RP - NOT IN FILE
NT - UI - 99023143LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - CLINICAL
TRIALPT - CONTROLLED CLINICAL TRIALPT - JOURNAL ARTICLEID - DA05938/DA/NIDAID -
DA06275/DA/NIDAID - DA10217/DA/NIDAID - +DA - 19981120IS - 0140-6736SB - ASB -
MSB - XCY - ENGLANDJC - L0SAA - AuthorEM - 199901RO - M:LC1RO - M:LC2
UR - PM:0009807990
SO - Lancet 1998 Oct
31 ;352(9138):1433-1437
77
UI - 74
AU - Morgan MJ
AD - Department of
Psychology, University of Wales, Swansea, S. Wales, UK
TI - Recreational
use of "ecstasy" (MDMA) is associated with elevated impulsivity
AB - Recent
preclinical evidence suggests that repeated exposure to 3, 4-
methylenedioxy-methamphetamine (MDMA; "ecstasy") produces long-term
reductions in serotonin (5-HT) levels. 5-HT has been implicated in the
regulation of mood, anxiety, aggression, impulsivity, and cognition.
Accordingly, in the first of two separate studies, these variables were
investigated in three groups: (1) MDMA group--recreational ecstasy users (who
also used other illicit substances); (2) polydrug controls-- who had never
taken ecstasy, but otherwise had drug histories and personal characteristics
similar to the ecstasy users; and (3) nondrug controls--who had never used
illicit drugs, but had similar personal characteristics. All participants
completed mood (Likert) scales, personality questionnaires (which included the
impulsiveness, venturesomeness and empathy questionnaire-IVE), spatial span and
"Tower of London" (TOL) tests, and a behavioural measure of
impulsivity, the matching familiar figures test (MFF20). There were no group
differences in mood, anxiety, anger/hostility, and cognitive performance, but
the MDMA group committed significantly more errors in the MFF20. Subsequently,
a larger sample of participants were administered mood (the General Health
Questionnaire or GHQ) and personality (IVE) questionnaires before the
administration of a TOL test, followed by the MFF20, and a second TOL test.
Although there were no group differences in TOL performance, ecstasy users were
again found to commit more errors in the MFF20 than polydrug users.
Furthermore, the GHQ and IVE scores of the ecstasy users in the second study
indicated, respectively, that they were more psychologically disturbed and
impulsive than nondrug controls. The combined data from the two studies
indicated that ecstasy users exhibited elevated impulsivity on both self-report
and behavioral measures and that those who had taken the most ecstasy had the
most elevated trait impulsiveness scores. These findings are consistent with
previous evidence that elevated levels of impulsivity in humans are associated
with reduced levels of serotonergic function
MH - Adult
MH - Affect
MH - drug effects
MH - Cognition
MH - Comparative
Study
MH - Female
MH - Hallucinogens
MH - pharmacology
MH - Human
MH - Impulsive
Behavior
MH - chemically
induced
MH - psychology
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Questionnaires
MH -
Substance-Related Disorders
RP - NOT IN FILE
NT - UI - 98384701LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - CLINICAL TRIALPT - JOURNAL
ARTICLEDA - 19981125IS - 0893-133XSB - MCY - UNITED STATESJC - ADQAA - AuthorEM
- 199901
UR - PM:0009718589
SO -
Neuropsychopharmacology 1998 Oct ;19(4):252-264
78
UI - 90
AU - Morimoto BH
AU - Lovell S
AU - Kahr B
AD - AMUR
Pharmaceuticals, San Carlos, CA 94070, USA. morimoto@amur.com
TI - Ecstasy:
3,4-methylenedioxymethamphetamine (MDMA)
AB - The crystal
structure of 3,4-methylenedioxymethamphetamine [systematic name:
N-methyl-1-[3,4-(methylenedioxy) phenyl]-2-aminopropane] hydrochloride,
C11H15NO2.HCl, also known as 'ecstasy' or MDMA, has been determined by X-ray
diffraction
MH - Crystallization
MH -
Crystallography,X-Ray
MH - Hallucinogens
MH - chemistry
MH - Hydrogen
Bonding
MH -
Models,Molecular
MH - Molecular
Structure
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Support,Non-U.S.Gov't
MH - Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 98201023LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19980424IS -
0108-2701SB - MCY - DENMARKJC - AI5AA - AuthorEM - 199807
UR - PM:0009540200
SO - Acta
Crystallogr C 1998 Feb 15 ;54 ( Pt 2)():229-231
79
UI - 64
AU - Muck-Seler D
AU - Takahashi S
AU - Diksic M
AD - Cone Laboratory
for Neurosurgical Research, Department of Neurology and Neurosurgery, and
Montreal Neurological Institute, McGill University, 3801 University St.,
Montreal, Quebec, Canada
TI - The effect of
MDMA (3,4-methylenedioxymethamphetamine) on the 5-HT synthesis rate in the rat
brain: an autoradiographic study
AB - The effect of
MDMA (3,4-methylenedioxymethamphetamine), a psychotropic amphetamine
derivative, treatment on the rate of serotonin (5- hydroxytryptamine; 5-HT)
synthesis in the rat brain was studied by autoradiography using
alpha-[14C]-methyl-l-tryptophan method. Three different treatment protocols
were compared to the control (saline) treated rats: (1) rats treated twice with
10 mg/kg every 12 h (20 mg/kg total) and injected tracer for the synthesis
measurements 15 h later; (2) rats treated with four injections of 5 mg/kg every
12 h (20 mg/kg total) and injected tracer for the synthesis measurement 17 h
after the last dose; and (3) rats given eight injections of 5 mg/kg every 12 h for
four days (40 mg/kg) and used in the synthesis study 14 days after the last
dose. Results showed a significant decrease in the rate of synthesis in the
majority of cerebral structures examined in the 10 mg/kg group. In contrast the
group receiving the same total amount (20 mg/kg) of MDMA but over two days (4x5
mg/kg) showed a significant increase in 5-HT synthesis in comparison to
controls. The 5-HT synthesis rates measured 14 days after the last dose (four
days, 8x5 mg/kg) were significantly reduced. The findings suggest that MDMA can
produce either an increase or a decrease in the 5-HT synthesis a short time
after a total dose of 20 mg/kg depending on the dose fractionation. However, 14
days after total dose of 40 mg/kg given over four days the synthesis rate was
significantly reduced in many brain structures. The latter suggests a possible
effect of the MDMA neurotoxicity on the serotonergic neurons, in addition to a
possible influence on 5-HT synthesis via a feedback mechanism. Copyright 1998
Elsevier Science B.V
MH - Algorithms
MH - Animal
MH - Autoradiography
MH - Brain
MH - anatomy &
histology
MH - Brain Chemistry
MH - drug effects
MH - Kinetics
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - Rats
MH - Rats,Sprague-Dawley
MH - Rats,Wistar
MH - Serotonin
MH - biosynthesis
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
MH - Tryptophan
MH - blood
MH - metabolism
RP - NOT IN FILE
NT - UI - 99032894LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 73-22-3
(Tryptophan)PT - JOURNAL ARTICLEID - RO1-NS-29629/NS/NINDSDA - 19990129IS -
0006-8993SB - MCY - NETHERLANDSJC - B5LAA - AuthorEM - 199904
UR - PM:0009813249
SO - Brain Res 1998
Nov 9 ;810(1-2):76-86
80
UI - 70
AU - O'Shea E
AU - Granados R
AU - Esteban B
AU - Colado MI
AU - Green AR
AD - Departamento de
farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
TI - The
relationship between the degree of neurodegeneration of rat brain 5- HT nerve
terminals and the dose and frequency of administration of MDMA ('ecstasy')
AB - The effect of
varying the dose and frequency of administration of 3,4-
methylenedioxymethamphetamine (MDMA or 'ecstasy') on both the acute
hyperthermic response and the long term neurodegeneration of 5-
hydroxytryptamine (5-HT) nerve terminals in the brain has been studied in Dark
Agouti rats. A single injection (4-15 mg/kg i.p.) of MDMA produced immediate
dose-related hyperthermia and a dose-related decrease in 5-HT,
5-hydroxyindoleacetic acid (5-HIAA) and [3H]paroxetine binding in regions of
the brain 7 days later, with a dose of 4 mg/kg having no degenerative effect.
This dose was also without effect when given once daily for 4 days, but
produced a marked loss of [3H]paroxetine binding and indole concentration (
approximately 55%) when given twice daily for 4 days. When a dose of 4 mg/kg
was given twice weekly for 8 weeks it had no effect on these serotoninergic
markers, despite a clear anorectic effect of the drug being seen. These data
demonstrate that MDMA-induced neurodegeneration is related to both the dose and
frequency of administration and indicate that damage to 5- HT neurones can
occur in the absence of a hyperthermic response to the drug. We suggest that
damage occurs when endogenous free radical scavenging mechanisms become
overwhelmed or exhausted
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - Brain
MH - metabolism
MH - pathology
MH - Cerebral Cortex
MH - Corpus Striatum
MH - Dose-Response
Relationship,Drug
MH - Drug
Administration Schedule
MH - Hippocampus
MH -
Hydroxyindoleacetic Acid
MH -
Injections,Intraperitoneal
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Nerve
Degeneration
MH - chemically
induced
MH - Nerve Endings
MH - Paroxetine
MH -
pharmacokinetics
MH - Rats
MH - Rats,Inbred
Strains
MH - Serotonin
MH - Serotonin
Agents
MH - Support,Non-U.S.Gov't
MH - Tissue
Distribution
RP - NOT IN FILE
NT - UI - 98447282LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 54-16-0
(Hydroxyindoleacetic Acid)RN - 61869-08-7 (Paroxetine)PT - JOURNAL ARTICLEDA -
19990107IS - 0028-3908SB - MCY - ENGLANDJC - NZBAA - AuthorEM - 199903
UR - PM:0009776387
SO -
Neuropharmacology 1998 Jul ;37(7):919-926
81
UI - 83
AU - Obradovic T
AU - Imel KM
AU - White SR
AD - Department of
Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington
State University, Pullman, WA 99164, USA
TI - Repeated
exposure to methylenedioxymethamphetamine (MDMA) alters nucleus accumbens
neuronal responses to dopamine and serotonin
AB - The purpose of
this experiment was to investigate the effects of repeated exposure to
methylenedioxymethamphetamine (MDMA) on responses of neurons in the nucleus
accumbens of anesthetized rats to microiontophoretically-applied dopamine and
serotonin. In tests conducted 1-4 days or 9-15 days following the last
injection of MDMA (20 mg/kg, s.c., twice daily for 4 days), the inhibitory
effects of both dopamine and serotonin on glutamate-evoked firing of nucleus
accumbens cells were significantly attenuated compared to effects in control
rats that were pretreated with saline injections. The inhibitory effect of the
D1 receptor agonist SKF38393 was also significantly attenuated in the
MDMA-pretreated rats. In contrast, the amount of inhibition of glutamate-evoked
firing produced by application of GABA did not significantly differ between the
MDMA-pretreated and the saline-pretreated rats. The neurotoxicity of the MDMA
treatment regimen was confirmed by demonstrating that 3H-paroxetine binding was
significantly decreased in the medial prefrontal cortex and the nucleus
accumbens of the MDMA-pretreated rats. The mechanisms that produce the
attenuated inhibitory responses to dopamine and serotonin following repeated
injections of MDMA are not known. However, the results of these experiments
indicate that repeated MDMA administration induces long-lasting changes in
dopaminergic as well as serotonergic neurotransmission in the nucleus
accumbens. Copyright 1998 Elsevier Science B.V
MH - Animal
MH - Dopamine
MH - pharmacology
MH - Drug
Administration Schedule
MH - Evoked
Potentials
MH - drug effects
MH - Glutamic Acid
MH - Gaba
MH -
Injections,Subcutaneous
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - administration
& dosage
MH - Neurons
MH - physiology
MH - Nucleus
Accumbens
MH - Rats
MH -
Rats,Sprague-Dawley
MH -
Receptors,Dopamine D1
MH - agonists
MH - Serotonin
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
MH - Sk&F-38393
MH - Time Factors
RP - NOT IN FILE
NT - UI - 98195323LA
- EngRN - 0 (Receptors, Dopamine D1)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6
(Dopamine)RN - 56-12-2 (GABA)RN - 56-86-0 (Glutamic Acid)RN - 67287-49-4
(SK&F-38393)PT - JOURNAL ARTICLEID - DA08116/DA/NIDADA - 19980529IS -
0006-8993SB - MCY - NETHERLANDSJC - B5LAA - AuthorEM - 199808
UR - PM:0009526029
SO - Brain Res 1998
Feb 23 ;785(1):1-9
82
UI - 87
AU - Parrott AC
AD - Faculty of
Science and Health, Department of Psychology, University of East London, UK.
andy2@uel.ac.uk
TI - The
psychobiology of MDMA or 'ecstasy': symposium arranged by the Psychobiology
Section, at the Annual Conference of the British Psychological Society,
Heriot-Watt University, Edinburgh, April 1997
MH - Animal
MH - Cognition
MH - drug effects
MH - Emotions
MH - Female
MH - Hallucinogens
MH - pharmacology
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neurons
MH - physiology
MH - Street Drugs
RP - NOT IN FILE
NT - UI - 98244365LA
- EngRN - 0 (Hallucinogens)RN - 0 (Street Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - CONGRESSESDA - 19980623IS -
0269-8811SB - MCY - UNITED STATESJC - CPHEM - 199808
UR - PM:0009584974
SO - J
Psychopharmacol 1998 ;12(1):97-102
83
UI - 88
AU - Parrott AC
AU - Lees A
AU - Garnham NJ
AU - Jones M
AU - Wesnes K
AD - Department of
Psychology, University of East London, UK. andy2@uel.ac.uk
TI - Cognitive
performance in recreational users of MDMA of 'ecstasy': evidence for memory
deficits
AB - Cognitive task
performance was assessed in three groups of young people: 10 regular users of
3,4-methylenedioxymethamphetamine (MDMA) who had taken 'ecstasy' 10 times or
more; 10 novice MDMA users who had taken 'ecstasy' one to nine times; and 10
control subjects who had never taken MDMA. A computerized battery of cognitive
tasks (Cognitive Drug Research system) was undertaken on a day when subjects were
drug free. Performance on the response speed and vigilance measures (simple
reaction time, choice reaction time, number vigilance), was similar across the
three subgroups. However on immediate word recall and delayed word recall, both
groups of MDMA users recalled significantly less words than controls. Animal
research has shown that MDMA can lead to serotonergic neurodegeneration,
particularly in the hippocampus and frontal cortex. Although the design of this
study was far from ideal, these data are consistent with other findings of
memory decrements in recreational MDMA users, possibly caused by serotonergic
neurotoxicity
MH - Adolescence
MH - Adult
MH - Analysis of
Variance
MH - Cognition
MH - drug effects
MH - Female
MH - Hallucinogens
MH - pharmacology
MH - Human
MH - Male
MH - Memory
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Reaction Time
MH - Street Drugs
RP - NOT IN FILE
NT - UI - 98244362LA
- EngRN - 0 (Hallucinogens)RN - 0 (Street Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19980623IS -
0269-8811SB - MCY - UNITED STATESJC - CPHAA - AuthorEM - 199808
UR - PM:0009584971
SO - J
Psychopharmacol 1998 ;12(1):79-83
84
UI - 69
AU - Parrott AC
AU - Lasky J
AD - Department of
Psychology, University of East London, UK. andy2@uel.ac.uk
TI - Ecstasy (MDMA)
effects upon mood and cognition: before, during and after a Saturday night
dance
AB - Three groups of
young people (aged 19-30 years) were compared: 15 regular ecstasy users who had
taken MDMA (3,4- methylenedioxymethamphetamine) on ten or more occasions; 15
novice ecstasy users who had taken MDMA on fewer than ten previous occasions;
and 15 controls who had never taken MDMA. Each subject completed a cognitive
test and mood scale battery four times: an initial drug-free baseline, at a
Saturday night dance/club (on-drug), then 2 days later, and 7 days later. On
the Saturday night, regular ecstasy users took an average of 1.80 MDMA tablets,
novice users took 1.45 MDMA tablets, while controls mostly drank alcohol. The
consumption of cannabis and cocaine at the club was similar across groups. All
three groups reported positive moods at the dance club (on-drug), although
there were borderline trends (P < 0.10) for less sadness/depression in the
MDMA subgroups. However 2 days afterwards, the ecstasy users felt significantly
more depressed, abnormal, unsociable, unpleasant, and less good tempered, than
the controls. Cognitive performance on both tasks (verbal recall, visual
scanning) was significantly reduced on- MDMA. Memory recall was also
significantly impaired in drug-free MDMA users, with regular ecstasy users
displaying the worst memory scores at every test session. This agrees with
previous findings of memory impairments in drug-free ecstasy users. Animal data
have shown that MDMA can generate long-term serotonergic neurodegeneration in
various brain areas, including the hippocampus. The cognitive deficits in drug-
free recreational ecstasy users, suggest that MDMA may also be neurotoxic in
humans
MH - Adult
MH - Affect
MH - drug effects
MH - Analysis of
Variance
MH - Cognition
MH - Dancing
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - pharmacology
MH - Human
MH - Male
MH - Memory
MH - Memory
Disorders
MH - chemically
induced
MH -
N-Methyl-3,4-methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 98455404LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19981228IS -
0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199903
UR - PM:0009784083
SO -
Psychopharmacology (Berl) 1998 Oct ;139(3):261-268
85
UI - 71
AU - Sabol KE
AU - Seiden LS
AD - University of
Mississippi, Department of Psychology, 301 Peabody Bldg., University, MS 38677,
USA
TI - Reserpine
attenuates D-amphetamine and MDMA-induced transmitter release in vivo: a
consideration of dose, core temperature and dopamine synthesis
AB - Amphetamine
releases dopamine through a transporter-mediated mechanism. The purpose of this
report was to further our understanding of the intracellular pool from which
amphetamine releases dopamine: the cytoplasmic pool, the vesicular pool, or
both. Rats were treated with D- amphetamine (AMPH) (1.0 or 10.0 mg/kg) or an
amphetamine analog, methylenedioxymethamphetamine (MDMA) (2.0, 5.0, or 10.0
mg/kg). Pre- treatment with 10.0 mg/kg reserpine (18 h prior to AMPH or MDMA)
attenuated dopamine release for high and low AMPH doses; however the low-dose
effect showed borderline significance. Pre-treatment with 10.0 mg/kg reserpine
attenuated dopamine and serotonin release induced by MDMA. The dopamine effect
was seen at all three MDMA doses; the effect on serotonin was only measured at
the 10.0 mg/kg dose. Reserpine pre- treatment caused reductions in core body
temperature; heating the rats to normal body temperature for 3 h prior to AMPH
or MDMA, and during the 4 h post-treatment period partially reversed the
reserpine-induced attenuation of dopamine release. However, the intermediate
level of dopamine release for the reserpinized-heated animals was not
significantly different from either the reserpine group (not heated) or the
AMPH or MDMA alone groups. In a separate group of rats, the effects of
reserpine and reserpine+heat on dopamine synthesis were measured. DOPA
accumulation after treatment with the aromatic acid decarboxylase inhibitor
NSD-1015 (100 mg/kg, 30 min before sacrifice), was greater in rats treated with
reserpine compared to controls; heating the reserpinized rats did not
significantly alter the amount of DOPA accumulation; however there was a trend
towards further increase. These results suggest that D-amphetamine releases
dopamine that is stored in both vesicles and the cytoplasm. Cooling may
contribute to the attenuation of AMPH or MDMA-induced dopamine release observed
after reserpine; however, AMPH or MDMA dependence upon vesicular stores most
likely explains the diminished release after reserpine. The attenuation of AMPH
or MDMA-induced transmitter release by reserpine is thought to be counteracted
by a reserpine-induced replenishment of stores. Therefore, all doses of
D-amphetamine may use vesicular stores; the degree to which new synthesis
counteracts the vesicular depletion may be the variable which differentiates
low from high doses of D- amphetamine. Copyright 1998 Elsevier Science B.V
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - physiology
MH -
Dextroamphetamine
MH - pharmacology
MH - Dopamine
MH - biosynthesis
MH - Dopamine Agents
MH - Dose-Response
Relationship,Drug
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Neurotransmitters
MH - metabolism
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Reserpine
MH - Serotonin
Agents
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 98413063LA
- EngRN - 0 (Dopamine Agents)RN - 0 (Neurotransmitters)RN - 0 (Serotonin
Agents)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-55-5
(Reserpine)RN - 51-61-6 (Dopamine)RN - 51-64-9 (Dextroamphetamine)PT - JOURNAL
ARTICLEID - DA00085/DA/NIDADA - 19981120IS - 0006-8993SB - MCY - NETHERLANDSJC
- B5LAA - AuthorEM - 199901
UR - PM:0009739110
SO - Brain Res 1998
Sep 21 ;806(1):69-78
86
UI - 93
AU - Schechter MD
AD - Department of
Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown
44272-0095, USA
TI - MDMA-like
stimulus effects of hallucinogens in male Fawn-Hooded rats
AB - A two-lever,
food-motivated, operant technique was employed to train the purportedly
serotonergically dysfunctional Fawn-Hooded (FH) rat to discriminate 1.5 mg/kg
MDMA. Once all 10 male subjects learned the MDMA- vehicle discrimination at
criterion performance level, doses different than the training dose were used
to generate a dose-response discrimination gradient. The ED50 value of MDMA was
shown to be 0.136 mg/kg, not significantly different from that of previously
trained Sprague-Dawley male rats. Thus, the Fawn-Hooded rat appears to not
differ in its sensitivity to lower doses of MDMA. Testing for MDMA-like
stimulus generalizations with other drugs indicated that the MDMA derivative
MDE produced generalization at a dose of 2.25 mg/kg and allowed for an ED50
value of 0.496 mg/kg. Like MDE, the testing of alpha-ethyltryptamine was shown
to produce MDMA-like responding. Lastly, a dose of 0.12 mg/kg LSD produced 90%
MDMA-lever selection. In contrast to MDMA generalizations to these three drugs,
testing of cocaine at doses of 2.5-10 mg/kg and mescaline at 8-14 mg/kg did not
produce MDMA-like discriminative effects. The results of this testing in the
presumably serotonergically dysfunctional Fawn-Hooded rat would indicate that
this line not only can discriminate MDMA as well as heterogenous-bred lines,
but also shows the same discriminative generalizations and nongeneralizations
from MDMA to serotonergic and dopaminergic agents
MH - Animal
MH - Central Nervous
System Stimulants
MH - pharmacology
MH -
Conditioning,Operant
MH - drug effects
MH - Cues
MH - Discrimination
(Psychology)
MH - Dopamine Agents
MH - Dose-Response
Relationship,Drug
MH -
Generalization,Stimulus
MH - Hallucinogens
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH - Rats,Inbred
Strains
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH - genetics
MH - physiology
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 98135835LA
- EngRN - 0 (Central Nervous System Stimulants)RN - 0 (Dopamine Agents)RN - 0
(Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - JOURNAL
ARTICLEDA - 19980331IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM
- 199806
UR - PM:0009476968
SO - Pharmacol
Biochem Behav 1998 Feb ;59(2):265-270
87
UI - 85
AU - Schechter MD
AD - Department of
Pharmacology, Northeastern Ohio Universities College of Medicine, Rootstown
44272-0095, USA. mds@neou-com.edu
TI -
'Candyflipping': synergistic discriminative effect of LSD and MDMA
AB - The
co-administration of D-lysergic acid diethylamide (LSD; 'Acid') and
3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy'; 'XTC'), has reached a
prevalence that has allowed for the street terminology 'candyflipping' to
describe the combination. Internet sites indicate a significant enhancement of
central effects with their simultaneous use. In this preliminary observation,
male Fawn-Hooded rats were trained to discriminate 1.5 mg/kg MDMA and were,
subsequently, tested with doses of MDMA (0.15 mg/kg) or LSD (0.04 mg/kg) that
each produced a saline- like response. Co-administration of these doses of MDMA
and LSD synergized to produce a maximal MDMA-like response. The possible
mechanism for synergistic action upon central serotonergic neurons is discussed
to explain the observed effect
MH - Animal
MH - Behavior,Animal
MH - drug effects
MH - Discrimination
Learning
MH - Drug Synergism
MH - Hallucinogens
MH - administration
& dosage
MH - pharmacology
MH - Lysergic Acid
Diethylamide
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH - Serotonin
Agents
RP - NOT IN FILE
NT - UI - 98202230LA
- EngRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-37-3 (Lysergic Acid Diethylamide)PT
- JOURNAL ARTICLEDA - 19980521IS - 0014-2999SB - MCY - NETHERLANDSJC - EN6AA -
AuthorEM - 199807
UR - PM:0009543229
SO - Eur J Pharmacol
1998 Jan 12 ;341(2-3):131-134
88
UI - 86
AU - Scheffel U
AU - Szabo Z
AU - Mathews WB
AU - Finley PA
AU - Dannals RF
AU - Ravert HT
AU - Szabo K
AU - Yuan J
AU - Ricaurte GA
AD - Department of
Radiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205,
USA
TI - In vivo
detection of short- and long-term MDMA neurotoxicity--a positron emission
tomography study in the living baboon brain
AB - The present
study evaluated short- and long-term effects of MDMA (3,4-
methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN
5652, a potent 5-HT transporter ligand, as well as [11C]RTI- 55, a cocaine
derivative which labels both 5-HT and dopamine transporters. Following baseline
PET scans with [11C](+)McN5652, [11C](- )McN5652 (the inactive enantiomer of
the active enantiomer [11C](+)McN5652) and [11C]RTI-55, a baboon was treated
with MDMA (5 mg/kg, s.c., twice daily for four consecutive days). PET studies
at 13, 19, and 40 days post-MDMA revealed decreases in mean radioactivity
levels in all brain regions when using [11C](+)McN 5652, but not with
[11C](-)McN5652 or [11C]RTI-55. Reductions in specific [11C](+)McN5652 binding
(calculated as the difference in radioactivity concentrations between (+) and
(-)[11C]McN5652) ranged from 44% in the pons to 89% in the occipital cortex.
PET studies at 9 and 13 months showed regional differences in the apparent
recovery of 5-HT transporters, with increases in some brain regions (e.g.,
hypothalamus) and persistent decreases in others (e.g., neocortex). Data obtained
from PET studies correlated well with regional 5-HT axonal marker
concentrations in the CNS measured after sacrifice of the animal. The results
of these studies indicate that PET imaging of the living nonhuman primate brain
with [11C](+)McN5652 can detect changes in regional 5-HT transporter density
secondary to MDMA-induced neurotoxicity. Using PET, it should also be feasible
to use [11C](+)McN5652 to determine whether human MDMA users are also
susceptible to MDMA's neurotoxic effects
MH - Animal
MH - Autoradiography
MH - Brain
MH - radionuclide
imaging
MH - Brain Chemistry
MH - drug effects
MH - Brain Diseases
MH - chemically
induced
MH - Carbon Isotopes
MH - Carrier
Proteins
MH - metabolism
MH - Cocaine
MH - analogs &
derivatives
MH - diagnostic use
MH - Iodine
Radioisotopes
MH - Isoquinolines
MH - Male
MH - Membrane
Glycoproteins
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Papio
MH - Radioligand
Assay
MH - Serotonin
Agents
MH - Serotonin
Antagonists
MH -
Support,U.S.Gov't,P.H.S.
MH -
Tomography,Emission-Computed
RP - NOT IN FILE
NT - UI - 98253940LA
- EngRN - 0 (serotonin transporter)RN - 0 (Carbon Isotopes)RN - 0 (Carrier
Proteins)RN - 0 (Iodine Radioisotopes)RN - 0 (Isoquinolines)RN - 0 (Membrane
Glycoproteins)RN - 0 (Serotonin Agents)RN - 0 (Serotonin Antagonists)RN -
133647-95-7 (RTI 55)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN
- 50-36-2 (Cocaine)RN - 96795-90-3 (McN 5652)PT - JOURNAL ARTICLEID - DA
06309/DA/NIDAID - DA 10217/DA/NIDAID - DA 06275/DA/NIDADA - 19980701IS -
0887-4476SB - MCY - UNITED STATESJC - VFLAA - AuthorEM - 199809
UR - PM:0009593108
SO - Synapse 1998
Jun ;29(2):183-192
89
UI - 68
AU - Schifano F
AU - Di Furia L
AU - Forza G
AU - Minicuci N
AU - Bricolo R
AD - Addiction
Treatment Unit No. 1 (SerT 1), Padova, Italy. schifano@ux1.unipd.it
TI - MDMA
('ecstasy') consumption in the context of polydrug abuse: a report on 150
patients
AB - The present
study examined the characteristics and the possible psychopathological
consequences of ecstasy (MDMA, 3,4- methylenedioxymethamphetamine) use. One
hundred and fifty consecutive patients, presenting to the Padova (Italy)
Addiction Treatment Unit and who had taken ecstasy on at least one occasion,
were examined and studied using a semi-structured interview. Ninety-five
percent of the patients had experimented with another drug of abuse at least
once in their lifetime. Ecstasy was mainly self-administered at disco clubs,
and reported acute psychoactive effects confirmed previous reports. Fifty-three
percent of the total sample were found to be affected by one or more
psychopathological problems; the most frequent were depression, psychotic
disorders, cognitive disturbances, bulimic episodes, impulse control disorders,
panic disorders, social phobia. Those who were free from any psychopathological
problem, compared to the others, had taken a smaller number of MDMA tablets in
their lifetime, for a shorter duration and with a lower frequency. Again, they
were less likely to have used alcohol together with ecstasy but more likely to
have used opiates. Longer-term, larger dosage (acute or cumulative) MDMA
consumers were found to be at high risk of developing psychopathological
disturbances. The results are discussed, taking into account both the ecstasy
suggested serotonin (5-hydroxytryptamine) neurotoxicity and the various
methodological issues pertaining to this kind of large-scale clinical study
describing people for whom MDMA is far from being the only drug of abuse
MH - Adult
MH - Comparative
Study
MH - Dose-Response
Relationship,Drug
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Male
MH - Mental
Disorders
MH - chemically
induced
MH - psychology
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Retrospective
Studies
MH - Serotonin
MH - metabolism
MH - Street Drugs
MH -
Substance-Related Disorders
MH - Time Factors
RP - NOT IN FILE
NT - UI - 99004279LA
- EngRN - 0 (Hallucinogens)RN - 0 (Street Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - JOURNAL
ARTICLEDA - 19981230IS - 0376-8716SB - MCY - IRELANDJC - EBSAA - AuthorEM -
199903
UR - PM:0009788011
SO - Drug Alcohol
Depend 1998 Sep 1 ;52(1):85-90
90
UI - 67
AU - Shankaran M
AU - Gudelsky GA
AD - College of
Pharmacy, University of Cincinnati, OH 45267-0004, USA
TI - Effect of
3,4-methylenedioxymethamphetamine (MDMA) on hippocampal dopamine and serotonin
AB - The
3,4-methylenedioxymethamphetamine (MDMA)-induced increase in the extracellular
concentration of dopamine and the long-term depletion of 5-HT were studied in
the hippocampus of the rat brain. MDMA produced a dose-dependent increase in
the extracellular concentration of dopamine in the hippocampus, as well as in
the striatum. The MDMA-induced increase in the extracellular concentration of
dopamine in the hippocampus, but not in the striatum, was suppressed in rats
treated with the norepinephrine uptake inhibitor, desipramine, and in rats in
which noradrenergic neurons in the hippocampus were lesioned with DSP4 (N-(2-
chloroethyl)-N-ethyl-2-bromo benzylamine). However, the long- term depletion of
5-HT in the hippocampus produced by MDMA was unaltered in desipramine-treated
rats. These results are supportive of the view that the MDMA-induced increase
in the extracellular concentration of dopamine in the hippocampus is the result
of an enhanced release of dopamine from noradrenergic neurons. In addition, the
MDMA-induced depletion of 5-HT in the hippocampus appears not to involve
dopamine-initiated processes, because suppression of MDMA- induced dopamine
release did not attenuate the long-term depletion of 5- HT in the hippocampus
MH - Adrenergic
Uptake Inhibitors
MH - pharmacology
MH - Animal
MH - Desipramine
MH - Dopamine
MH - metabolism
MH - Dose-Response
Relationship,Drug
MH - Hippocampus
MH - drug effects
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 99017829LA
- EngRN - 0 (Adrenergic Uptake Inhibitors)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-47-5 (Desipramine)RN - 50-67-9
(Serotonin)RN - 51-61-6 (Dopamine)PT - JOURNAL ARTICLEID - DA07427/DA/NIDADA -
19990301IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 199905
UR - PM:0009802829
SO - Pharmacol
Biochem Behav 1998 Dec ;61(4):361-366
91
UI - 75
AU - Vollenweider FX
AU - Gamma A
AU - Liechti M
AU - Huber T
AD - Psychiatric
University Hospital Zurich, Research Department, Zurich, Switzerland
TI - Psychological
and cardiovascular effects and short-term sequelae of MDMA
("ecstasy") in MDMA-naive healthy volunteers [see comments]
AB - 3,
4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational
drug reported to produce a different psychological profile than that of classic
hallucinogens and stimulants. It has, therefore, been tentatively classified
into a novel pharmacological class termed entactogens. This double-blind
placebo-controlled study examined the effects of a typical recreational dose of
MDMA (1.7 mg/kg) in 13 MDMA- naive healthy volunteers. MDMA produced an
effective state of enhanced mood, well-being, and increased emotional
sensitiveness, little anxiety, but no hallucinations or panic reactions. Mild
depersonalization and derealization phenomena occurred together with moderate
thought disorder, first signs of loss of body control, and alterations in the
meaning of percepts. Subjects also displayed changes in the sense of space and
time, heightened sensory awareness, and increased psychomotor drive. MDMA did
not impair selective attention as measured by the Stroop test. MDMA increased
blood pressure moderately, with the exception of one subject who showed a
transient hypertensive reaction. This severe increase in blood pressure
indicates that the hypertensive effects of MDMA, even at recreational doses,
should not be underestimated, particularly in subjects with latent
cardiovascular problems. Most frequent acute somatic complaints during the MDMA
challenge were jaw clenching, lack of appetite, impaired gait, and restless
legs. Adverse sequelae during the following 24 hours included lack of energy
and appetite, feelings of restlessness, insomnia, jaw clenching, occasional
difficulty concentrating, and brooding. The present findings are consistent
with the hypothesis that MDMA produces a different psychological profile than
classic hallucinogens or psychostimulants
MH - Adult
MH - Affect
MH - drug effects
MH - Anorexia
MH - chemically
induced
MH - Blood Pressure
MH - Body
Temperature
MH - Bruxism
MH - Comparative
Study
MH - Double-Blind
Method
MH - Fatigue
MH - Female
MH - Hallucinogens
MH - adverse effects
MH - Human
MH - Male
MH - Middle Age
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Reaction Time
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 98384700LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - CLINICAL TRIALPT - JOURNAL
ARTICLEDA - 19981125IS - 0893-133XSB - MCY - UNITED STATESJC - ADQAA - AuthorEM
- 199901RO - M:LC2
UR - PM:0009718588
SO -
Neuropsychopharmacology 1998 Oct ;19(4):241-251
92
UI - 82
AU - Zheng Y
AU - Laverty R
AD - Department of
Pharmacology, University of Otago, P.O. Box 913, Dunedin, New Zealand
TI - Role of brain
nitric oxide in (+/-)3,4-methylenedioxymethamphetamine (MDMA)-induced
neurotoxicity in rats
AB - The role of nitric
oxide (NO) in the long-term serotoninergic neurotoxicity induced by
(+/-)3,4-methylenedioxymethamphetamine (MDMA) in rats was investigiated.
Pretreatment with Nomega-nitro-L-arginine (L- NOARG) (10 mg kg-1), a nitric
oxide synthase (NOS) inhibitor, partially protected against long-term serotonin
(5-HT) depletion induced by MDMA (40 mg kg-1) in frontal cortex and parietal
cortex, but not in other brain regions examined. Brain NOS activities in these
two regions were significantly elevated at 6 h after MDMA administration.
Moreover, L- NOARG pretreatment caused significant inhibition of brain NOS
activity but did not affect the acute 5-HT and dopamine (DA) changes or the
hyperthermia induced by MDMA. These results suggest that it is the NOS
inhibitory properties of L-NOARG, rather than its effects on the acute
monoamine changes or the hyperthermia induced by MDMA, that are responsible for
the prevention of neurotoxicity. The regional differences on the protection of
L-NOARG and on the activation of NOS by MDMA indicate the unequal role that NO
may play in MDMA-induced neurotoxicity in different brain regions. Copyright
1998 Elsevier Science B.V. All rights reserved
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - Enzyme
Activation
MH - Enzyme Inhibitors
MH - pharmacology
MH -
Hydroxyindoleacetic Acid
MH - metabolism
MH - Indazoles
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Nerve
Degeneration
MH - chemically
induced
MH - enzymology
MH - Nerve Tissue
Proteins
MH - Nitric Oxide
MH - physiology
MH - Nitric-Oxide
Synthase
MH - Nitroarginine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 98288185LA
- EngRN - EC 1.14.13.- (neural constitutive nitric oxide synthase)RN - EC
1.14.13.39 (Nitric-Oxide Synthase)RN - 0 (Enzyme Inhibitors)RN - 0
(Indazoles)RN - 0 (Nerve Tissue Proteins)RN - 0 (Serotonin Agents)RN -
10102-43-9 (Nitric Oxide)RN - 2149-70-4 (Nitroarginine)RN - 2942-42-9
(7-nitroindazole)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN -
50-67-9 (Serotonin)RN - 54-16-0 (Hydroxyindoleacetic Acid)PT - JOURNAL
ARTICLEDA - 19980819IS - 0006-8993SB - MCY - NETHERLANDSJC - B5LAA - AuthorEM -
199810
UR - PM:0009622646
SO - Brain Res 1998
Jun 8 ;795(1-2):257-263
93
UI - 102
AU - Baker LE
AU - Virden TB
AU - Miller ME
AU - Sullivan CL
AD - Department of
Psychology, Western Michigan University, Kalamazoo 49008, USA
TI - Time course
analysis of the discriminative stimulus effects of the optical isomers of
3,4-methylenedioxymethamphetamine (MDMA)
AB - The present
study examined the discriminative stimulus effects of the MDMA optical isomers
administered at different presession injection intervals. In the first
experiment, male Sprague-Dawley rats were trained in a two-lever,
food-reinforced operant procedure to discriminate either (+)-MDMA (1.25 mg/kg)
or (-)-MDMA (3.50 mg kg) at either 20 or 90 min following injection. Animals
administered (+)-MDMA or saline 90 min before training sessions failed to
attain the discrimination criteria after 73 training sessions, whereas (-)-MDMA
successfully established discriminative stimulus control at both the 20 min and
the 90 min postinjection intervals. (+)-Amphetamine did not substitute for
either isomer, although a significant amount of drug- appropriate responding
occurred in animals trained to discriminate (+)- MDMA at 20 min and (-)-MDMA at
90 min. Sch 39166 partially reduced the discrimination of (+)-MDMA at 20 min
and (-)-MDMA at 90 min, although this effect was not dose dependent. Sch 39166
had no effect on animals trained to discriminate (-)-MDMA at 20 min.
Haloperidol did not alter the discrimination of (+)-MDMA at 20 min but
partially reduced the discriminative stimulus control of (-)-MDMA at 20 min and
(-)-MDMA at 90 min. Fenfluramine substituted for both isomers of MDMA.
Pirenpirone completely blocked the discriminative stimulus effects of (-)-MDMA
at 20 min, although (+)-MDMA at 20 min and (-)-MDMA at 90 min were only partly
blocked. WAY 100,135 had little effect on drug-appropriate responding; however,
the discrimination of (+)-MDMA at 20 min was partly reduced by this 5-HT1A
antagonist. In a second experiment, rats trained to discriminate (+)-MDMA (1.5
mg/kg) or (-)-MDMA (3.0 mg/kg) from saline were administered substitution tests
with both isomers 20, 60, 90 and 120 min after injection. Results confirmed
those of the first experiment that (+)-MDMA appears to have a shorter duration
of action than (-)-MDMA. These results are discussed in light of the training
doses employed
MH - Amphetamine
MH - pharmacology
MH - Animal
MH - Discrimination
(Psychology)
MH - drug effects
MH - Dose-Response
Relationship,Drug
MH - Hallucinogens
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Stereoisomerism
MH - Time Factors
RP - NOT IN FILE
NT - UI - 97444080LA
- EngRN - 0 (Hallucinogens)RN - 300-62-9 (Amphetamine)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19971201IS -
0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 199802
UR - PM:0009300612
SO - Pharmacol
Biochem Behav 1997 Oct ;58(2):505-516
94
UI - 105
AU - Baker LE
AU - Taylor MM
AD - Department of
Psychology, Western Michigan University, Kalamazoo 49008, USA
TI - Assessment of
the MDA and MDMA optical isomers in a stimulant- hallucinogen discrimination
AB - The
phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and
3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants
and hallucinogens in drug discrimination investigations. The stereoisomers of
these compounds, in particular those of MDA, appear to produce differential effects.
Previous studies have demonstrated that animals trained to discriminate
amphetamine from vehicle generalize to the S(+)-isomers but not the
R(-)-isomers of MDA and MDMA while animals trained to discriminate LSD from
saline generalize to R(-)-MDA and neither isomer of MDMA. However, animals
trained to discriminate mescaline from vehicle generalize to both stereoisomers
of these phenylisopropylamine derivatives. The present study consisted of two
experiments in which a three-choice drug discrimination procedure was employed
to compare the stereoisomers of MDA and MDMA to both amphetamine and either
mescaline (experiment one) or LSD (experiment two). Sixteen male Sprague-Dawley
rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and mescaline (12.5
mg/kg) and eight rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg)
and LSD (0.08 mg/kg) from saline in three-choice, food reinforced drug
discrimination procedures. Substitution tests were administered with the
isomers of MDA and MDMA. In the second experiment, substitution tests were also
administered with lower doses of each training compound and with the stimulant
cocaine and the hallucinogen 2,5-dimethoxy-4-methylphenylisopropylamine (DOM).
In both experiments, all of the isomers produced very few responses on the
S(+)- amphetamine lever. In the first experiment, R(-)-MDA and R(-)-MDMA
produced nearly complete substitution for mescaline. The results of the second
experiment revealed partial substitution for LSD with both isomers of MDMA and
S(+)-MDA, and nearly complete substitution with R(- )MDA for LSD. The present
findings do not support previous reports that S(+)-MDMA and S(+)-MDMA
substitute for S(+)-amphetamine. The three- lever drug discrimination procedure
may provide a more sensitive behavioral assay in which to examine the
discriminative stimulus effects of drugs with compound stimulus properties
MH - Animal
MH - Cocaine
MH - pharmacology
MH - Discrimination
Learning
MH - drug effects
MH - physiology
MH - Dom
MH - Food
MH - Generalization
(Psychology)
MH - Hallucinogens
MH - Lysergic Acid
Diethylamide
MH - Male
MH - Mescaline
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Narcotics
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Reinforcement
(Psychology)
MH - Stereoisomerism
MH -
3,4-Methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 97403645LA
- EngRN - 0 (Hallucinogens)RN - 0 (Narcotics)RN - 15588-95-1 (DOM)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 50-36-2 (Cocaine)RN - 50-37-3 (Lysergic
Acid Diethylamide)RN - 54-04-6 (Mescaline)PT - JOURNAL ARTICLEDA - 19971016IS -
0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 199712
UR - PM:0009259001
SO - Pharmacol
Biochem Behav 1997 Aug ;57(4):737-748
95
UI - 109
AU - Cohen RS
AU - Cocores J
AD - Fairleigh
Dickinson, University Madison, New Jersey, USA
TI -
Neuropsychiatric manifestations following the use of 3,4-
methylenedioxymethamphetamine (MDMA: "Ecstasy")
AB - 1. The
recurring side-effects associated with MDMA consumption are reviewed. 2. The
recreational use of "Ecstasy" has been implicated in the onset of
various psychological, neurological, and organic complications. A table has
been employed to depict the deleterious reactions that have occurred following
MDMA ingestion. 3. An original case report is presented in which an individual
developed perpetual neuropsychiatric symptomatology after having consumed MDMA.
This case indicates that MDMA may induce long lasting effects, even after one
exposure
MH - Adolescence
MH - Brain Diseases
MH - chemically
induced
MH - Case Report
MH - Human
MH - Male
MH - Mental
Disorders
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Time Factors
RP - NOT IN FILE
NT - UI - 97337413LA
- EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL
ARTICLEDA - 19970917IS - 0278-5846SB - MCY - ENGLANDJC - Q45AA - AuthorEM -
199711
UR - PM:0009194153
SO - Prog
Neuropsychopharmacol Biol Psychiatry 1997 May ;21(4):727-734
96
UI - 106
AU - Colado MI
AU - O'Shea E
AU - Granados R
AU - Murray TK
AU - Green AR
AD - Departamento de
Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
TI - In vivo
evidence for free radical involvement in the degeneration of rat brain 5-HT
following administration of MDMA ('ecstasy') and p- chloroamphetamine but not
the degeneration following fenfluramine
AB - 1.
Administration of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') to
several species results in a long lasting neurotoxic degeneration of
5-hydroxytryptaminergic neurones in several regions of the brain. We have now
investigated whether this degeneration is likely to be the result of free
radical-induced damage. 2. Free radical formation can be assessed by measuring
the formation of 2,3- and 2,5- dihydroxybenzoic acid (2,3-DHBA and 2,5-DHBA)
from salicylic acid. An existing method involving implantation of a probe into
the hippocampus and in vivo microdialysis was modified and validated. 3.
Administration of MDMA (15 mg kg-1, i.p.) to Dark Agouti (DA) rats increased
the formation of 2,3-DHBA (but not 2,5-DHBA) for at least 6 h. Seven days after
this dose of MDMA, the concentration of 5-hydroxytryptamine (5- HT) and 5-hydroxyindoleacetic
acid (5-HIAA) was reduced by over 50% in hippocampus, cortex and striatum,
reflecting neurotoxic damage. There was no change in the concentration of
dopamine or 3,4- dihydroxyphenylacetic acid (DOPAC) in the striatum. 4. p-
Chloroamphetamine (PCA), another compound which produces a neurotoxic loss of
cerebral 5-HT content, when given at a dose of 5 mg kg-1 also significantly
increased the formation of 2.3-DHBA (but not 2,5-DHBA) in the dialysate for
over 4.5 h. post-injection starting 2 h after treatment. 5. In contrast,
fenfluramine administration (15 mg kg-1, i.p.) failed to increase the 2,3-DHBA
or 2,5-DHBA concentration in the dialysate. A single fenfluramine injection
nevertheless also markedly decreased the concentration of 5-HT and 5-HIAA in
the hippocampus, cortex and striatum seven days later. 6. When rats pretreated
with fenfluramine (15 mg kg-1, i.p.) seven days earlier were given MDMA (15 mg
kg-1, i.p.) no increase in 2,3-DHBA was seen in the dialysate from the
hippocampal probe. This indicates that the increase in free radical formation
following MDMA is occurring in 5-HT neurones which have been damaged by the
prior fenfluramine injection. 7. Administration of the free radical scavenging
agent alpha-phenyl-N-tert-butyl nitrone (PBN; 120 mg kg-1, i.p.) 10 min before
and 120 min after an MDMA (15 mg kg-1, i.p.) injection prevented the acute rise
in the 2,3-DHBA concentration in the dialysate and attenuated by 30% the long
term damage to hippocampal 5-HT neurones (as indicated by a smaller
MDMA-induced decrease in both the concentration of 5-HT and 5-HIAA and also the
binding of [3H]-paroxetine). 8. These data indicate that a major mechanism by
which MDMA and PCA induce damage to 5- hydroxytryptaminergic neurones in rat
brain is by increasing the formation of free radicals. These probably result
from the degradation of catechol and quinone metabolites of these substituted
amphetamines. In contrast, fenfluramine induces damage by another mechanism not
involving free radicals; a proposal supported by some of our earlier indirect
studies. 9. We suggest that these different modes of action render untenable
the recent suggestion that MDMA will not be neurotoxic in humans because
fenfluramine appears safe at clinical doses
MH - p-Chloroamphetamine
MH - toxicity
MH - Animal
MH - Biogenic
Monoamines
MH - metabolism
MH - Body
Temperature
MH - drug effects
MH - Brain Chemistry
MH - Fenfluramine
MH - Free Radical
Scavengers
MH - pharmacology
MH - Free Radicals
MH - Hippocampus
MH - Male
MH - Microdialysis
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nerve
Degeneration
MH - Paroxetine
MH - Rats
MH - Serotonin
Agents
MH - Serotonin
Uptake Inhibitors
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 97365718LA
- EngRN - 0 (Biogenic Monoamines)RN - 0 (Free Radical Scavengers)RN - 0 (Free
Radicals)RN - 0 (Serotonin Agents)RN - 0 (Serotonin Uptake Inhibitors)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 458-24-2
(Fenfluramine)RN - 61869-08-7 (Paroxetine)RN - 64-12-0 (p-Chloroamphetamine)PT
- JOURNAL ARTICLEDA - 19970915IS - 0007-1188SB - MCY - ENGLANDJC - B00AA -
AuthorEM - 199711
UR - PM:0009222545
SO - Br J Pharmacol
1997 Jul ;121(5):889-900
97
UI - 108
AU - Colado MI
AU - O'Shea E
AU - Granados R
AU - Misra A
AU - Murray TK
AU - Green AR
AD - Departamento de
Farmacologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
TI - A study of the
neurotoxic effect of MDMA ('ecstasy') on 5-HT neurones in the brains of mothers
and neonates following administration of the drug during pregnancy
AB - 1. It is well
established that 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') is
neurotoxic and produces long term degeneration of cerebral 5-hydroxytryptamine
(5-HT) nerve terminals in many species. Since MDMA is used extensively as a
recreational drug by young people, it is being ingested by many women of child
bearing age. We have therefore examined the effect of administering high doses
of MDMA to rats during pregnancy on the cerebral content of both the dams and
the neonates. 2. MDMA (20 mg kg-1, s.c.) was injected twice daily on days 14-17
of the gestation period. The initial dose produced a marked hyperthermic
response in the dam which was progressively attenuated in both peak height and
area under the curve following further doses of the drug. The body weight of
the dams decreased during the period of treatment. 3. There was a modest
decrease in litter size (-20%) of the MDMA-treated dams. 4. The concentration
of 5-HT and its metabolite 5- HIAA was decreased by over 65% in the hippocampus
and striatum and 40% in the cortex of the dams 1 week after parturition. In
contrast, the content of 5-HT and 5-HIAA in the dorsal telencephalon of the
pups of the MDMA-treated dams was the same as that seen in tissue from pups
born to control animals. 5. Administration of MDMA (40 mg kg-1, s.c.) to adult
rats increased thiobarbituric acid reacting substances (TBARS) in cortical
tissue 3 h and 6 h later, indicating increased lipid peroxidation. No increase
in TBARS was seen in the cortical tissue of 7- 10 day neonates injected with
this dose of MDMA 3 h or 6 h earlier. 6. The data suggest that exposure to MDMA
in utero during the maturation phase does not produce damage to 5-HT nerve
terminals in the foetal rat brain, in contrast to the damage seen in the brains
of the mothers. This may be due to MDMA being metabolized to free radical
producing entities in the adult brain but not in the immature brain or,
alternatively, to more effective or more active free radical scavenging
mechanisms being present in the immature brain
MH - Animal
MH - Body
Temperature
MH - drug effects
MH - Body Weight
MH - Brain
MH - Dopamine
MH - metabolism
MH - Female
MH -
Hydroxyindoleacetic Acid
MH - Lipid
Peroxidation
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - Neurons
MH - Pregnancy
MH - Rats
MH - Rats,Wistar
MH - Serotonin
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 97351873LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN - 51-61-6
(Dopamine)RN - 54-16-0 (Hydroxyindoleacetic Acid)PT - JOURNAL ARTICLEDA -
19970925IS - 0007-1188SB - MCY - ENGLANDJC - B00AA - AuthorEM - 199711
UR - PM:0009208155
SO - Br J Pharmacol
1997 Jun ;121(4):827-833
98
UI - 103
AU - Curran HV
AU - Travill RA
AD - Department of
Psychology, University College London, UK. v.curran@ucl.ac.uk
TI - Mood and
cognitive effects of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'):
week-end 'high' followed by mid-week low
AB - AIMS:
Recreational use of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is
widespread. The present study aimed to examine both the acute and residual
effects of this drug on users' mood and cognitive function. DESIGN AND
PARTICIPANTS: A parallel group design was used to compare 12 participants who
reported having taken MDMA with 12 participants who reported having consumed
only alcohol, on the relevant night (day 1). These same participants were then
re-assessed the following day (day 2) and again mid-week (day 5). FINDINGS:
Acute effects of MDMA broadly replicated previous findings. MDMA users rated
elevated mood on day 1 but significantly low mood on day 5, at which point some
participants scored within the range for clinical depression. In contrast, the
alcohol group showed less pronounced changes, which followed a U-shaped curve
over days with the lowest point being day 2. The MDMA group also showed
significant impairments on an attentional/working memory task, compared with
alcohol users. CONCLUSIONS: Weekend use of MDMA may lead to depressed mood
mid-week. Possible mechanisms underlying the findings are discussed in terms of
temporary depletion of serotonin, serotonergic neurotoxity and psychological
aspects of mood change
MH - Adult
MH - Affect
MH - drug effects
MH - Alcohol
Drinking
MH - psychology
MH - Cognition
MH - Comparative
Study
MH - Female
MH - Follow-Up
Studies
MH - Hallucinogens
MH - pharmacology
MH - Human
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Substance-Related Disorders
RP - NOT IN FILE
NT - UI - 97438553LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19970923IS -
0965-2140CY - ENGLANDJC - BM3AA - AuthorEM - 199711
UR - PM:0009293041
SO - Addiction 1997
Jul ;92(7):821-831
99
UI - 110
AU - De S
AU - Kelly JP
AU - Harkin AJ
AU - Leonard BE
AD - Department of
Pharmacology, University College, Galway, Ireland
TI - An appraisal of
the pharmacological and toxicological effects of a single oral administration
of 3,4-methylenedioxymethamphetamine (MDMA) in the rat
AB - This study
examined some acute pharmacological and toxicological effects of 3,4
methylenedioxymethamphetamine (MDMA, "Ecstasy") over a range of doses
(20, 40, 80, 160 and 320 mg/kg orally) in adult female rats. Deaths were
observed from the 40 mg/kg MDMA group onwards. Reductions in body weight
change, food and water intake were found in the 80 mg/kg group, whilst food
intake alone was reduced in the 20 and 40 mg/kg groups. Significant
hyperthermic responses were found over the first 8 hr following MDMA
administration which were dose-related. A significant hyperactivity of
approximately 9 hr duration was observed in the 20 mg/kg and 40 mg/kg groups,
whereas there was evidence of a serotonin syndrome in the higher dosage groups.
Thus, acute oral administration of MDMA results in a variety of measurable
responses. The cause of death in this study is probably a combination of
serotonin syndrome and hyperthermia
MH -
Administration,Oral
MH - Animal
MH - Body
Temperature
MH - Dose-Response
Relationship,Drug
MH - Drug
Administration Schedule
MH - Female
MH - Hallucinogens
MH - pharmacology
MH - toxicity
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Rectum
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 97325545LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19970718IS -
0901-9928SB - MCY - DENMARKJC - PHTAA - AuthorEM - 199709
UR - PM:0009181598
SO - Pharmacol
Toxicol 1997 May ;80(5):207-210
100
UI - 94
AU - Dinse H
AD - Abteilung fur
Anasthesiologie und Intensivmedizin, Berufsgenossenschaftliche Unfall-klinik
Tubingen
TI - [Ecstasy (MDMA)
intoxication. An overview]
AB - The increased
consumption of "ecstasy" (MDMA, 3,4-methylenedioxy- methamphetamine)
has also increased the number of life-threatening intoxications. From a Medline
search of the years 1992-1996, reports were registered and evaluated. Besides
cerebral, cardiorespiratory, renal, and hepatic symptoms, hyperthermia
syndromes such as malignant hyperthermia, neuroleptic malignant syndrome, or
the serotonin syndrome were common. In addition to a discussion of the
intoxication symptoms and their acute and intensive-care therapy, the
psychological and physiological effects of "ecstasy" will be described.
Some historical considerations of the topic are included in this review
MH - Emergency
Medical Services
MH - English
Abstract
MH - Hallucinogens
MH - pharmacology
MH - poisoning
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Overdose
MH - therapy
RP - NOT IN FILE
NT - UI - 97454907LA
- GerRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEPT - REVIEWPT -
REVIEW, TUTORIALDA - 19971119IS - 0003-2417SB - MCY - GERMANYJC - 4MYAA - AuthorEM
- 199801
UR - PM:0009382208
SO - Anaesthesist
1997 Aug ;46(8):697-703
101
UI - 119
AU - Frederick DL
AU - Paule MG
AD - Division of
Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR
72079-9502, USA
TI - Effects of MDMA
on complex brain function in laboratory animals
AB - This review
surveys experiments that have examined the effects of acute and chronic MDMA
exposure on schedule-controlled operant behaviors thought to engender responses
that reflect the expression of complex brain functions. Such functions include
time estimation, short-term memory, learning, motivation, and color and
position discrimination. Recent experiments conducted in the Behavioral
Toxicology Laboratory at the National Center for Toxicological Research concerning
MDMA's acute and long-term effects on rhesus monkey performance in an operant
test battery are compared to previous studies involving the effects of MDMA on
operant behaviors. Results of these experiments suggest that when given
acutely, MDMA disrupts complex brain functions associated with learning and
time estimation more than those associated with short-term memory and visual
discrimination, and that behavioral tasks requiring relatively high rates of
responding are particularly sensitive to the disruptive effects of MDMA.
Repeated exposure to doses of MDMA sufficient to produce long-lasting changes
in brain neurotransmitter systems results in residual effects (e.g. tolerance,
sensitivity) on behavioral task performance when subjects are subsequently
challenged with acute MDMA, whereas baseline (non-challenged) performance of
these tasks after such exposure generally remains unchanged. Although the
experiments described herein were conducted on a relatively small number of
non-human subjects, they raise the possibility that long-term effects on
cognitive processes may also occur in humans exposed to repeated or acute high
doses of MDMA
MH - Animal
MH - Brain
MH - drug effects
MH - physiology
MH - Dose-Response
Relationship,Drug
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 97147305LA
- EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL
ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19970411IS - 0149-7634SB - MCY -
UNITED STATESJC - OA7AA - AuthorEM - 199706
UR - PM:0008994210
SO - Neurosci
Biobehav Rev 1997 Jan ;21(1):67-78
102
UI - 91
AU - Gartside SE
AU - McQuade R
AU - Sharp T
AD - University of
Oxford Department of Clinical Pharmacology, Radcliffe Infirmary, UK
TI - Acute effects
of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and release:
comparison between dorsal and median raphe 5-HT systems
AB - It is proposed
that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more toxic to 5-HT
neurones projecting from the dorsal raphe nucleus (DRN) than to those from the
median raphe nucleus (MRN). Since increased 5-HT release has been associated
with MDMA-induced neurotoxicity, MDMA may have a DRN-selective 5-HT releasing
effect. Here we have compared the effects of acute MDMA on DRN and MRN 5-HT
pathways using in vivo electrophysiological and neurochemical techniques. MDMA
inhibited the firing of 5-HT neurones in both the DRN and the MRN, and did so
with similar potency (ED50 values, 0.589 +/- 0.151 (8) and 0.588 +/- 0.207 (6)
mg/kg i.v., respectively). In both nuclei this inhibitory effect was reversed
by the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.).
Microdialysis measurements were made in the frontal cortex and dorsal
hippocampus, regions which receive a DRN- and an MRN-selective 5-HT
innervation, respectively. A dose of 1 mg/kg i.v. MDMA increased extracellular
5-HT 3-fold in both the frontal cortex and dorsal hippocampus. A higher dose (3
mg/kg i.v.) increased 5-HT levels 8-fold in both regions. Overall, our data
suggest that MDMA releases 5-HT from the cell body and terminal regions of both
DRN and MRN 5-HT pathways, and does so in a qualitatively and quantitatively
similar fashion. We conclude that any DRN-selectivity in the neurotoxic effects
of MDMA is not due to a DRN- selective, acute 5-HT releasing action of the drug
MH -
Chromatography,High Pressure Liquid
MH - Comparative
Study
MH - Electric
Stimulation
MH -
Electrochemistry
MH -
Electrophysiology
MH - Hippocampus
MH - drug effects
MH - metabolism
MH - Microdialysis
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - Neurons
MH - Piperazines
MH - Prefrontal
Cortex
MH - Pyridines
MH - Raphe Nuclei
MH - cytology
MH - physiology
MH - Serotonin
MH - Serotonin
Agents
MH - Serotonin
Antagonists
MH - Stereotaxic
Techniques
MH -
Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 98176618LA
- EngRN - 0 (Piperazines)RN - 0 (Pyridines)RN - 0 (Serotonin Agents)RN - 0
(Serotonin Antagonists)RN - 146714-97-8 (WAY 100635)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - JOURNAL
ARTICLEDA - 19980505IS - 0028-3908SB - MCY - ENGLANDJC - NZBAA - AuthorEM -
199807
UR - PM:0009517441
SO -
Neuropharmacology 1997 Nov ;36(11-12):1697-1703
103
UI - 95
AU - Huether G
AU - Zhou D
AU - Ruther E
AD - Psychiatrische
Klinik, Universitat Gottingen, Federal Republic of Germany
TI - Causes and
consequences of the loss of serotonergic presynapses elicited by the
consumption of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy")
and its congeners
AB - The massive and
prolonged stimulation of serotonin (5-HT)-release and the increased
dopaminergic activity are responsible for the acute psychomimetic and
psychostimulatory effects of 3,4-methylenedioxy- methamphetamine (MDMA,
"ecstasy") and its congeners. In vulnerable subjects, at high doses
or repeated use, and under certain unfavorable conditions (crowding, high
ambient temperature), severe, in some cases fatal, averse systemic reactions
(hyperthermia, serotonin-syndrome) may occur during the first few hours. Animal
experiments revealed the existence of similar differences in vulnerability and
similar dose- and context-related influences on a similar sequence of acute
responses. The severity of these acute systemic responses is closely related to
the severity of the long-term damage to 5-HT axon terminals caused by the
administration of substituted amphetamines. Attempts to identify the mechanisms
involved in this selective degeneration of 5-HT presynapses brought to light a
multitude of different factors and conditions which either attenuate or
potentiate the loss of 5-HT terminals caused by MDMA and related amphetamine
derivatives. These puzzling observations suggest that the degeneration of 5-HT
presynapses represents only the final step in a sequence of events which
compromise the ability of 5-HT terminals to maintain their functional and
structural integrity. Substituted amphetamines selectively tax energy
metabolism in 5-HT presynapses through their ability to exchange with 5- HT and
to dissipate transmembrane ion gradients. The active carrier systems in the
vesicular and presynaptic membrane operate at a permanently activated state. The
resulting energy deficit can no longer adequately restored by the 5-HT
presynapses when their availability of substrates for ATP production is
additionally reduced by the hyperthermic and other energy consuming reactions
which are elicited by the systemic administration of substituted amphetamines.
The exhaustion of energy in 5-HT nerve terminals compromised all
energy-requiring endogenous mechanisms involved in the regulation of
transmembrane-ion exchange, internal Ca(++)-homeostasis, prevention of oxidative
stress, detoxification, and repair. Above a critical threshold the failure of
these self-protective mechanisms will lead to the degeneration of the 5- HT
axon terminals. Based on the role of 5-HT as a global modulatory
transmitter-system involved in the stabilization and integration of impulse
flow between distributed multifocal neuronal networks, the partial loss of 5-HT
presynapses must be expected to impair the ability of these networks to
maintain the integrity of signal flow pattern, and increase the likelihood of
switching to unstable information processing. Behavioral responding may
therefore become more dominated by activities generated in individual networks,
and hitherto "buffered" personality traits and predisposition may
become manifested as defined psychiatric syndromes in certain predisposed
subjects
MH -
Amphetamine-Related Disorders
MH - metabolism
MH - pathology
MH - physiopathology
MH - Animal
MH - Energy
Metabolism
MH - drug effects
MH - Hallucinogens
MH - administration
& dosage
MH - pharmacology
MH - toxicity
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - analogs &
derivatives
MH - Nerve
Degeneration
MH - Presynaptic
Terminals
MH - Serotonin
MH -
Support,Non-U.S.Gov't
MH - Synaptic
Transmission
RP - NOT IN FILE
NT - UI - 98113680LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)PT - JOURNAL
ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19980226IS - 0300-9564SB - MCY - AUSTRIAJC
- CIJAA - AuthorEM - 199804
UR - PM:0009451711
SO - J Neural Transm
1997 ;104(8-9):771-794
104
UI - 116
AU - Kikura R
AU - Nakahara Y
AU - Mieczkowski T
AU - Tagliaro F
AD - National
Institute of Health Sciences, Tokyo, Japan
TI - Hair analysis
for drug abuse. XV. Disposition of 3, 4- methylenedioxymethamphetamine (MDMA)
and its related compounds into rat hair and application to hair analysis for
MDMA abuse
AB - In order to
clarify the mechanism of drug incorporation into hair, disposition of
3,4-methylenedioxyamphetamine (MDA), 3,4- methylenedioxymethamphetamine (MDMA),
3,4- methylenedioxyethylamphetamine (MDEA), 3-methoxy-4,5-
methylenedioxyamphetamine (MMDA) and metabolites of MDMA, 4-hydroxy-3-
methoxyamphetamine (HMAP) and 4-hydroxy-3-methoxymethamphetamine (HMMA), into
hair was investigated with an animal model. After the intraperitoneal
administration of those six drugs to pigmented hairy rats (5 mg/kg/day, 10
days, n = 3), the parent compounds and their metabolites in the rat plasma (5,
15, 30, 60, 120, 360 min after administration) and in the newly grown rat hair
for 4 weeks were determined by GC/MS-SIM. When the ratio of hair concentration
to area under the concentration versus time curves (AUCs) in plasma was
represented as an index of incorporation rate (ICR) of drugs into hair, the
order of ICRs was HMAP < MDA < HMMA < MDMA < MDEA < MMDA. In the
comparison between MDA, MDMA and MDEA, their ICRs increased according to the
length of carbon branches from proton to ethyl at the N position. From the
point of view that the ICRs of MMDA was 2.3 times as much as that of MDA, the
methoxy group on the benzene ring seemed to serve as a positive factor for the
ICR. However, the ICRs of 4-hydroxy- 3-methoxy compounds, HMAP and HMMA, were lower
in comparison with those of MDA and MDMA, respectively. On the other hand, the
ICRs of MDA, MDMA and MDEA were 5.5-6.1 times larger than those of amphetamine,
methamphetamine and ethylamphetamine, suggesting that the methylenedioxy group
on the benzene ring raises their ICRs very positively. Moreover, in order to
apply the results from the animal experiments to human cases, the scalp hair
samples of seven MDMA abusers were analyzed. MDMA and its metabolites, MDA;
were simultaneously detected in all the samples by GC/MS. In the two samples,
MDEA was found in addition to MDMA and MDA. It was shown that a hair sample is
a good specimen for the confirmation of retrospective use of
methylenedioxyamphetamines
MH - Amphetamines
MH -
pharmacokinetics
MH - Animal
MH - Comparative
Study
MH - Hair
MH - metabolism
MH - Hallucinogens
MH - Human
MH - Lactates
MH - Male
MH - Mass
Fragmentography
MH - Methamphetamine
MH - analogs &
derivatives
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH - Substance Abuse
Detection
MH - methods
MH -
Substance-Related Disorders
MH -
3,4-Methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 97195370LA
- EngRN - 0 (Amphetamines)RN - 0 (Hallucinogens)RN - 0 (Lactates)RN -
117652-28-5 (4-hydroxy-3-methoxymethamphetamine)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 515-30-0 (atrolactic acid)RN - 537-46-2
(Methamphetamine)RN - 82801-81-8 (3,4-methylenedioxyethamphetamine)PT - JOURNAL
ARTICLEDA - 19970328IS - 0379-0738SB - MCY - IRELANDJC - F49AA - AuthorEM -
199706
UR - PM:0009042722
SO - Forensic Sci
Int 1997 Jan 17 ;84(1-3):165-177
105
UI - 118
AU - Koch S
AU - Galloway MP
AD - Department of
Psychiatry and Behavioral Neurosciences, Wayne State University School of
Medicine, Detroit, MI, USA
TI - MDMA induced
dopamine release in vivo: role of endogenous serotonin
AB - Acting as a
substrate at the serotonin (5-HT) transporter, (+)-MDMA
(3,4-methylenedioxymethamphetamine), is a potent releaser of 5-HT and causes
toxicity to 5-HT neurons after repeated exposure. (+)-MDMA also releases
dopamine (DA), although with less potency. Since we have shown previously that
the intrastriatal application of 5-HT facilities DA release, it was
hypothesized that increased release of striatal 5-HT after MDMA may influence
extracellular levels of DA. Using microdialysis in vivo, we found that (+)-MDMA
(4.7 mumol/kg, i.v.) administration increased extracellular striatal DA levels
to 501% of control (p < 0.01, n = 12). However, in the presence of
fluoxetine (14.4 mumol/kg, s.c.), which prevents (+)-MDMA effects on 5-HT
release, the (+)-MDMA-induced increase in DA was significantly less (to 375% of
control, p < 0.05, vs. no fluoxetine, n = 8). In vitro studies with striatal
slices, to test drug selectivity, showed that (+)-MDMA (0.3-3 microM) increased
extracellular levels of both DA and 5-HT in a dose- dependent manner.
Fluoxetine (3 microM) completely blocked the effects of (+)-MDMA on 5-HT
release, but did not alter (+)-MDMA-induced DA release in vitro. The selective
DA transport inhibitor GBR-12909 (1 microM), blocked (+)-MDMA's effect on DA
release. It is concluded that 5-HT release after (+)-MDMA treatment partially
contributes to (+)- MDMA's effect on DA release in vivo
MH - Animal
MH -
Chromatography,High Pressure Liquid
MH - Dopamine
MH - metabolism
MH - Dopamine Uptake
Inhibitors
MH - pharmacology
MH - Fluoxetine
MH - In Vitro
MH - Ketanserin
MH - Male
MH - Microdialysis
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Neostriatum
MH - drug effects
MH - Piperazines
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH - Serotonin
Agents
MH - Serotonin
Antagonists
MH - Serotonin
Uptake Inhibitors
MH -
Support,Non-U.S.Gov't
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 97346660LA
- EngRN - 0 (Dopamine Uptake Inhibitors)RN - 0 (Piperazines)RN - 0 (Serotonin
Agents)RN - 0 (Serotonin Antagonists)RN - 0 (Serotonin Uptake Inhibitors)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9 (Serotonin)RN -
51-61-6 (Dopamine)RN - 54910-89-3 (Fluoxetine)RN - 67469-78-7 (GBR 12909)RN -
74050-98-9 (Ketanserin)PT - JOURNAL ARTICLEID - NIDA-04120DA - 19970903IS -
0300-9564SB - MCY - AUSTRIAJC - CIJAA - AuthorEM - 199711
UR - PM:0009203077
SO - J Neural Transm
1997 ;104(2-3):135-146
106
UI - 104
AU - Kramer HK
AU - Poblete JC
AU - Azmitia EC
AD - Department of
Psychiatry, New York University Medical Center, NY 10016, USA
TI - Activation of
protein kinase C (PKC) by 3,4- methylenedioxymethamphetamine (MDMA) occurs
through the stimulation of serotonin receptors and transporter
AB - This report
further characterizes the intermediate metabolic effects of the psychotropic
amphetamine derivative, 3,4- methylenedioxymethamphetamine (MDMA or
"ecstasy"), on the activity of second messenger-dependent kinases.
Previous work has demonstrated that two injections of MDMA (20 mg/kg) elicits a
prolonged translocation of the calcium and phospholipid-dependent enzyme,
protein kinase C (PKC) in rats. However, because MDMA has actions at the 5-HT
transporter and 5-HT2A/2C receptors, our experiments were directed at
uncovering which of these many sites may be involved in this second messenger
dependent response. A single injection of MDMA produced a time- and dose-
dependent increase in the density of cortical and hippocampal PKC (as measured
by 3H-phorbol 12,13-dibutyrate (PDBu) binding sites. MDMA- mediated PKC
translocation was long-lasting and remained above control (saline-treated rats)
for up to 24 h after injection. This effect was mimicked by another substituted
amphetamine, p-chloroamphetamine (pCA), but with a temporal-response curve that
was to the left of MDMA's. However, pure uptake inhibitors like fluoxetine,
cocaine, and the selective 5-HT2A/2C agonist, DOB, were unable to produce a
long-lasting translocation of PKC binding sites in rat cortex. Fluoxetine, a
selective serotonin uptake inhibitor (SSRI) and ketanserin a 5-HT2A antagonist,
attenuated PKC translocation by MDMA with differing efficacies; however, both
compounds completely prevented the loss of 5- HT uptake sties after multiple
doses of MDMA. These results suggest that MDMA increases PKC translocation by
two interrelated mechanisms that involve 5-HT2A/2C receptors and the 5-HT
transporter. This pathway appears to include: (1) the drug binding to the 5-HT
transporter, (2) the release of cytosolic 5-HT stores into the extracellular
space, and (3) the activation of post-synaptic 5-HT2A/2C receptors linked to G-
protein-mediated phospholipid hydrolysis
MH - Animal
MH - Binding Sites
MH - Brain
MH - drug effects
MH - metabolism
MH - Brain Stem
MH - Carrier
Proteins
MH - Cerebral Cortex
MH - Comparative
Study
MH - Enzyme
Activation
MH - Female
MH - Fluoxetine
MH - pharmacology
MH - Hippocampus
MH - Ketanserin
MH - Membrane
Glycoproteins
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Phorbol
12,13-Dibutyrate
MH - Protein Kinase
C
MH - Rats
MH -
Rats,Sprague-Dawley
MH -
Receptors,Serotonin
MH - Serotonin
Agents
MH - Serotonin
Uptake Inhibitors
RP - NOT IN FILE
NT - UI - 97418518LA
- EngRN - EC 2.7.1.- (Protein Kinase C)RN - 0 (serotonin transporter)RN - 0
(Carrier Proteins)RN - 0 (Membrane Glycoproteins)RN - 0 (Receptors,
Serotonin)RN - 0 (Serotonin Agents)RN - 0 (Serotonin Uptake Inhibitors)RN -
37558-16-0 (Phorbol 12,13-Dibutyrate)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 54910-89-3 (Fluoxetine)RN -
74050-98-9 (Ketanserin)PT - JOURNAL ARTICLEDA - 19980108IS - 0893-133XSB - MCY
- UNITED STATESJC - ADQAA - AuthorEM - 199803
UR - PM:0009272479
SO -
Neuropsychopharmacology 1997 Sep ;17(3):117-129
107
UI - 111
AU - LeSage M
AU - Poling A
AD - Department of
Psychology, Western Michigan University, Kalamazoo 49008, USA
TI - MDMA and
d-amphetamine produce comparable effects in pigeons performing under a multiple
fixed-ratio interresponse-time-greater-than-t schedule of food delivery
AB - The purpose of
this study was to gain further information about the behavioral effects of
(+/-) 3.4-methylenedioxymethamphetamine (MDMA) on schedule-controlled
responding. MDMA (0.32, 0.56, 1.0, 3.2, 5.6, and 10 mg/kg) and d-amphetamine
(0.32, 0.56, 1.0, 3.2, 5.6, and 10 mg/kg) were administered to pigeons
performing under a multiple fixed-ratio 30 (FR 30)
interresponse-time-greater-than-15-s (IRT > 15-s) schedule of food delivery.
In general, both drugs had no significant effect on response rates under the
IRT > 15-s component at doses that decreased rates under the FR component.
Results of the present experiment indicate that under some conditions MDMA and
d-amphetamine produce similar, and rate- dependent, effects
MH - Animal
MH - Central Nervous
System Stimulants
MH - pharmacology
MH -
Conditioning,Operant
MH - drug effects
MH -
Dextroamphetamine
MH - Drug Screening
MH - Food
MH - Hallucinogens
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Pigeons
MH - Reaction Time
MH - Reinforcement
Schedule
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 97307378LA
- EngRN - 0 (Central Nervous System Stimulants)RN - 0 (Hallucinogens)RN -
42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 51-64-9
(Dextroamphetamine)PT - JOURNAL ARTICLEID - DA07869-01A4/DA/NIDADA - 19970730IS
- 0091-3057SB - MCY - UNITED STATESJC - P3QAA - AuthorEM - 199710
UR - PM:0009164569
SO - Pharmacol
Biochem Behav 1997 May ;57(1-2):173-177
108
UI - 117
AU - Lin HQ
AU - Jackson DM
AU - Atrens DM
AU - Christie MJ
AU - McGregor IS
AD - Department of
Pharmacology, University of Sydney, Australia
TI - Serotonergic
modulation of 3,4-methylenedioxymethamphetamine (MDMA)- elicited reduction of
response rate but not rewarding threshold in accumbal self-stimulation
AB - In a fixed
interval 5-s rate-frequency function paradigm with rats, 3,4-
methylenedioxymethamphetamine (MDMA; 0.5, 2 and 4 mg/kg) dose- dependently
decreased response rate for nucleus accumbens self- stimulation while both
D-amphetamine (0.3 and 1 mg/kg) and cocaine (5 and 15 mg /kg) increased
response rates. The highest doses of MDMA caused a cessation of responding in
many of the rats tested, but in those rats that continued to respond a
significant reduction in frequency threshold for self-stimulation was seen.
Cocaine and amphetamine dose-dependently reduced frequency threshold in all
rats tested. The non-specific serotonin antagonist, methysergide (5 mg/kg),
reversed the inhibitory effects of MDMA on response rates and caused all rats
to respond following MDMA (4 mg/kg). Methysergide did not affect MDMA's
threshold-lowering properties and when administered alone methysergide had not
effect on self-stimulation. These results suggest serotonergic involvement in
the performance but not reinforcement- modulating effect of MDMA in the
self-stimulation paradigm
MH - Animal
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - Nucleus
Accumbens
MH - drug effects
MH - Rats
MH - Rats,Wistar
MH - Reward
MH - Self
Stimulation
MH - Sensory
Thresholds
MH - Serotonin
MH - Support,Non-U.S.Gov't
RP - NOT IN FILE
NT - UI - 97179111LA
- EngRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)RN - 50-67-9
(Serotonin)PT - JOURNAL ARTICLEDA - 19970416IS - 0006-8993SB - MCY -
NETHERLANDSJC - B5LAA - AuthorEM - 199706
UR - PM:0009027397
SO - Brain Res 1997
Jan 9 ;744(2):351-357
109
UI - 100
AU - Mallick A
AU - Bodenham AR
AD - Academic Unit
of Anaesthesia, Leeds General Infirmary
TI - MDMA induced
hyperthermia: a survivor with an initial body temperature of 42.9 degrees C
AB - A young male
survived hyperpyrexia (42.9 degrees C) following MDMA ("Ecstasy")
ingestion. He developed convulsions, rhabdomyolysis, metabolic acidosis, and
respiratory failure. This was successfully managed by assisted ventilation,
aggressive fluid therapy, and the early administration of dantrolene, in
addition to cooling measures. This is the first report of a survivor with such
a severe hyperpyrexia
MH - Adult
MH - Blood Gas
Analysis
MH - Body
Temperature
MH - Case Report
MH - Dantrolene
MH - therapeutic use
MH - Emergency
Service,Hospital
MH - Fever
MH - chemically
induced
MH - diagnosis
MH - drug therapy
MH - Hallucinogens
MH - Human
MH - Male
MH - Muscle
Relaxants,Central
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Substance-Related Disorders
MH - complications
RP - NOT IN FILE
NT - UI - 97461666LA
- EngRN - 0 (Hallucinogens)RN - 0 (Muscle Relaxants, Central)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 7261-97-4 (Dantrolene)PT - JOURNAL
ARTICLEDA - 19971031IS - 1351-0622SB - MCY - ENGLANDJC - B0UAA - AuthorEM - 199801
UR - PM:0009315942
SO - J Accid Emerg
Med 1997 Sep ;14(5):336-338
110
UI - 97
AU - Mann H
AU - Ladenheim B
AU - Hirata H
AU - Moran TH
AU - Cadet JL
AD - Molecular
Neuropsychiatry Section, NIDA, Addiction Research Center, Baltimore, MD 21224,
USA
TI - Differential
toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine
(MDMA) in multidrug-resistant (mdr1a) knockout mice
AB - The toxic
effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and
methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic
systems were assessed in the striatum and of the nucleus accumbens in mdr1a
wild-type and knockout mice. METH caused significant dose-dependent decreases
of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus
accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH
(2.5 mg/kg) caused only small changes in the wild-type, but marked. decreases
in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused
similar changes in both strains of mice. In contrast to METH, MDMA caused
greater percentage decreases in DAT in the wild-type mice. For example, the
lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of
wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused
similar changes in both the strains. These results suggest that METH and MDMA
interact differentially with P- glycoproteins. These observations document, for
the first time, a role for these proteins in the entry of METH and MDMA into
the brain via the blood-brain barrier, with P-glycoprotein possibly
facilitating the entry of MDMA but interfering with that of METH into the brain
MH - Animal
MH - Binding Sites
MH - drug effects
MH - Corpus Striatum
MH - metabolism
MH - Dopamine
MH - Dose-Response
Relationship,Drug
MH - Genes,Mdr
MH - genetics
MH - Male
MH - Methamphetamine
MH - poisoning
MH - Mice
MH - Mice,Knockout
MH - Mice,Mutant
Strains
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nucleus
Accumbens
MH - Serotonin
Agents
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 98040360LA
- EngRN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 51-61-6 (Dopamine)RN - 537-46-2
(Methamphetamine)PT - JOURNAL ARTICLEID - HD 24605/HD/NICHDDA - 19971223IS -
0006-8993SB - MCY - NETHERLANDSJC - B5LAA - AuthorEM - 199802
UR - PM:0009374204
SO - Brain Res 1997
Sep 26 ;769(2):340-346
111
UI - 113
AU - Montgomery H
AU - Myerson S
TI - 3,4-methylenedioxymethamphetamine
(MDMA, or "ecstasy") and associated hypoglycemia [letter]
MH - Acute Disease
MH - Adult
MH - Case Report
MH - Dantrolene
MH - adverse effects
MH - Female
MH - Fever
MH - chemically
induced
MH - Hallucinogens
MH - poisoning
MH - Human
MH - Hypoglycemia
MH - Muscle
Relaxants,Central
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rhabdomyolysis
RP - NOT IN FILE
NT - UI - 97249064LA
- EngRN - 0 (Hallucinogens)RN - 0 (Muscle Relaxants, Central)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 7261-97-4 (Dantrolene)PT -
LETTERDA - 19970424IS - 0735-6757SB - MCY - UNITED STATESJC - AA2EM - 199706
UR - PM:0009115539
SO - Am J Emerg Med
1997 Mar ;15(2):218
112
UI - 99
AU - Nakahara Y
AU - Kikura R
AD - National
Institute of Health Sciences, Tokyo, Japan
TI - Hair analysis
for drugs of abuse. XVIII. 3,4- Methylenedioxymethamphetamine (MDMA) disposition
in hair roots and use in identification of acute MDMA poisoning
AB - Disposition of
3,4-methylenedioxymethamphetamine (MDMA) in hair roots was studied using rats
and the hair root samples were evaluated to prove acute MDMA poisoning. The
back hair of male pigmented hairy rats (n = 6) was shaved and 5 d later the
animals were intraperitoneally administered with acute poisonous doses (20, 40,
60, 80 and 100 mg/kg) of MDMA. Roots of the hairs were then plucked out with a
hair nipper 5 min and, 0.5, 1, 2, 6 and 24 h after injection. The hair root
samples were, directly or after being washed with detergent, extracted with
methanol-5 N HCl (20:1) under ultrasonication in ice-cold water for 4 h. After
filtration and evaporation, the residue was derivatized with pentafluoropropionic
anhydride and analyzed by GC/MS. From all samples including the 5 min sample,
MDMA was detected at high concentrations (up to 156 ng/mg) accompanied by
3,4-methylenedioxyamphetamine (MDA). Some of the animals died within 2 h after
administration, but in the surviving rats the MDMA concentrations in the hair
roots increased up to 6 h and then slowly decreased until 24 h. The remaining
MDMA after washing apparently increased from 13-31% at 0.5 h to 51-83% at 24 h
in the surviving rats. These facts show that most of drugs in the hair roots
are not yet immobilized in the early stage and are thereafter gradually
incorporated into the hair shaft. Increase of the MDMA concentration stopped
soon after death of the animal, probably due to the cessation of hair growth.
Although the ratios of MDA/MDMA steadily increased over time, those after death
plateaued, probably due to the cessation of metabolism after death. It was
clearly shown that MDMA is more quickly incorporated into and more firmly retained
in hair than methamphetamine (MA) by comparing their disposition in hair roots
MH - Acute Disease
MH - Animal
MH - Disease
Models,Animal
MH - Dose-Response
Relationship,Drug
MH - Hair
MH - chemistry
MH - Hallucinogens
MH - poisoning
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Rats
MH -
Substance-Related Disorders
MH - diagnosis
RP - NOT IN FILE
NT - UI - 97473094LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL ARTICLEDA - 19971201IS -
0918-6158SB - MCY - JAPANJC - BPZAA - AuthorEM - 199802
UR - PM:0009331978
SO - Biol Pharm Bull
1997 Sep ;20(9):969-972
113
UI - 107
AU - Poland RE
AU - Lutchmansingh P
AU - McCracken JT
AU - Zhao JP
AU - Brammer GL
AU - Grob CS
AU - Boone KB
AU - Pechnick RN
AD - Department of
Psychiatry, Harbor-UCLA Medical Center, Torrance 90509, USA
TI - Abnormal ACTH
and prolactin responses to fenfluramine in rats exposed to single and multiple
doses of MDMA
AB - The present
study examined the persistent functional consequences associated with exposure
to single and multiple doses of (+/-) 3,4- methylenedioxymethamphetamine (MDMA)
as reflected by the neuroendocrine responses to d,l-fenfluramine (FEN). Adult
male rats were administered a single dose of MDMA (20 mg/kg, s.c.) and
challenged 2 weeks later with saline or FEN (2, 4, 6 and 8 mg/kg, s.c.). The
corticotropin (ACTH) response to FEN (6 and 8 mg/kg) was blunted and the
prolactin response to FEN (4 and 6 mg/kg) was enhanced in MDMA pre-treated
rats. The ACTH and prolactin responses to FEN (6 mg/kg, s.c.) were then
evaluated 4, 8 and 12 months after exposure to single and multiple doses MDMA
(20 mg/kg, s.c. and 20 mg/kg, s.c., bid, x 4 days, respectively). The ACTH
response to FEN was significantly reduced at 4 and 8 months in both MDMA
treatment groups, and at 12 months in the multiple dose group only. In
contrast, the prolactin response to FEN was enhanced in both groups of MDMA
treated rats at 4 months, but only in the multiple dose group at 8 months. By
12 months, the prolactin response to FEN had normalized. Following multiple
doses of MDMA, 5-HT concentrations were reduced significantly in the frontal
cortex at 4 and 12 months. The results indicate that exposure to single or
multiple doses of MDMA can produce functional alterations which can persist for
months, whereas the biochemical sequelae were less robust and shorter lived
MH - Animal
MH - Cerebral Cortex
MH - drug effects
MH - Corticotropin
MH - blood
MH - metabolism
MH - Dose-Response
Relationship,Drug
MH - Fenfluramine
MH - pharmacology
MH - Hallucinogens
MH - Hippocampus
MH - Hypothalamus
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Prolactin
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Serotonin
MH - Serotonin
Agents
MH -
Support,U.S.Gov't,P.H.S.
RP - NOT IN FILE
NT - UI - 97370396LA
- EngRN - 0 (Hallucinogens)RN - 0 (Serotonin Agents)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 458-24-2 (Fenfluramine)RN -
50-67-9 (Serotonin)RN - 9002-60-2 (Corticotropin)RN - 9002-62-4 (Prolactin)PT -
JOURNAL ARTICLEID - DA06863/DA/NIDAID - MH00534/MH/NIMHID - MH00722/MH/NIMHDA -
19970827IS - 0033-3158SB - MCY - GERMANYJC - QGIAA - AuthorEM - 199710
UR - PM:0009226745
SO -
Psychopharmacology (Berl) 1997 Jun ;131(4):411-419
114
UI - 101
AU - Schwartz RH
AU - Miller NS
AD - University of
Virginia School of Medicine, Charlottesville, Virginia, USA
TI - MDMA (ecstasy)
and the rave: a review
MH - Adolescence
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - pharmacology
MH - poisoning
MH - diagnosis
MH - therapy
MH - Street Drugs
MH - Substance Abuse
Detection
RP - NOT IN FILE
NT - UI - 97456227LA
- EngRN - 0 (Street Drugs)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT
- JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19971014IS - 0031-4005SB
- ASB - MCY - UNITED STATESJC - OXVEM - 199712
UR - PM:0009310529
SO - Pediatrics 1997
Oct ;100(4):705-708
115
UI - 115
AU - Simantov R
AU - Tauber M
AD - Department of
Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
TI - The abused drug
MDMA (Ecstasy) induces programmed death of human serotonergic cells
AB - The widely
abused amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA, also called
"ecstasy") induces hallucination and psychostimulation, as well as
long-term neuropsychiatric behaviors such as panic and psychosis. In rodents
and monkeys, MDMA is cytotoxic to serotonergic neurons, but this is less clear
with humans. Herein, MDMA was cytotoxic to human serotonergic JAR cells; it
altered the cell cycle, increased G2/M phase arrest, and induced DNA
fragmentation in a cycloheximide-sensitive way. This apoptosis was not observed
in nonserotonergic human NMB cells. The stereospecific effect of amphetamines
in JAR cells, and the key role of NO and dopamine in MDMA- induced apoptosis
were determined. The relevancy of MDMA-induced cell death to drug users is
discussed
MH - Apoptosis
MH - drug effects
MH - Catecholamines
MH - physiology
MH - Cell Cycle
MH - Cell Survival
MH - Choriocarcinoma
MH - DNA
Fragmentation
MH - Female
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - toxicity
MH - Nitric Oxide
MH - Serotonin
Agents
MH -
Support,Non-U.S.Gov't
MH - Tumor
Cells,Cultured
MH - Uterine
Neoplasms
RP - NOT IN FILE
NT - UI - 97192137LA
- EngRN - 0 (Catecholamines)RN - 0 (Serotonin Agents)RN - 10102-43-9 (Nitric
Oxide)RN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL
ARTICLEDA - 19970311IS - 0892-6638SB - MSB - XCY - UNITED STATESJC - FASAA -
AuthorEM - 199705
UR - PM:0009039956
SO - FASEB J 1997
Feb ;11(2):141-146
116
UI - 112
AU - Spatt J
AU - Glawar B
AU - Mamoli B
TI - A pure amnestic
syndrome after MDMA ("ecstasy") ingestion [letter]
MH -
Administration,Oral
MH - Adult
MH - Amnesia
MH - chemically
induced
MH - Case Report
MH - Female
MH - Globus Pallidus
MH - pathology
MH - Hallucinogens
MH - poisoning
MH - Human
MH - Magnetic
Resonance Imaging
MH -
N-Methyl-3,4-methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 97252590LA
- EngRN - 0 (Hallucinogens)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)PT - LETTERDA - 19970424IS -
0022-3050SB - MCY - ENGLANDJC - JBBEM - 199706
UR - PM:0009120467
SO - J Neurol
Neurosurg Psychiatry 1997 Apr ;62(4):418-419
117
UI - 114
AU - Thomasius R
AU - Schmolke M
AU - Kraus D
AD - Psychiatrische
und Nerven- und Poliklinik der Universitat Hamburg
TI - [MDMA
("Ecstasy") use--an overview of psychiatric and medical sequelae (see
comments)]
AB - Epidemiological
research and Substance Abuse Warning Systems point to a sharp increase in the
use of "Ecstasy" (MDMA), as well as to structural changes in the drug
scene in and outside Europe. For some consumers, "Ecstasy" opens the
door to the abuse of other illegal substances. Since the mid-eighties
psychiatric complications and consequences of the abuse of MDMA have been
reported in at least 48 cases. It is necessary to differentiate between acute
psychiatric complications, which subside completely when the level of
intoxication comes down, toxic psychoses and long-term psychiatric diseases as
a consequence of substance abuse. The latter involve atypical and paranoid
psychoses, depressions, panic disorders, depersonalisation and behavioural
disorders. Convulsive seizures are among the most common problems involving the
central nervous system. Furthermore, there have been reports on cerebrovascular
accidents and intracranial haemorrhages. Literature reports on at least 53
cases of medical complications in abusers of MDMA, 14 of which came to a lethal
end. Research still blatantly lacks prospective epidemiological and clinical
studies on a sufficiently large scale to identify different developments of
dependency and predictors of harmful and unhealthy consumption
MH - Brain
MH - drug effects
MH - English
Abstract
MH - Human
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - adverse effects
MH - Neurologic Examination
MH -
Psychoses,Substance-Induced
MH - diagnosis
MH - psychology
MH - Seizures
MH - chemically
induced
MH -
Substance-Related Disorders
RP - NOT IN FILE
NT - UI - 97240864LA
- GerRN - 42542-10-9 (N-Methyl-3,4-methylenedioxyamphetamine)PT - JOURNAL
ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19970522IS - 0720-4299SB - MCY -
GERMANYJC - F67AA - AuthorEM - 199707RO - M:CNR
UR - PM:0009157047
SO - Fortschr Neurol
Psychiatr 1997 Feb ;65(2):49-61
118
UI - 72
AU - Tretter F
TI - [Entactogenic
drugs "ecstasy" (MDMA), "eve" (MDE) and other ring-
substituted methamphetamine derivatives. A new class of substances among
illegal designer drugs? (letter; comment)]
MH - Designer Drugs
MH - adverse effects
MH - Human
MH - Methamphetamine
MH - analogs &
derivatives
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH -
Psychoses,Substance-Induced
MH - etiology
MH - Risk Factors
MH -
3,4-Methylenedioxyamphetamine
RP - NOT IN FILE
NT - UI - 98403276LA
- GerRN - 0 (Designer Drugs)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 4764-17-4
(3,4-Methylenedioxyamphetamine)RN - 537-46-2 (Methamphetamine)PT - COMMENTPT -
LETTERDA - 19981028IS - 0028-2804SB - MCY - GERMANYJC - NWSEM - 199901RO -
M:CNR
UR - PM:0009732739
SO - Nervenarzt 1997
Nov ;68(11):922-923
119
UI - 98
AU - Yeh SY
AD - Molecular
Neuropsychiatry Section, National Institute on Drug Abuse, National Institute
of Health, Baltimore, MD 21224, USA
TI - Effects of
salicylate on 3,4-methylenedioxymethamphetamine (MDMA)- induced neurotoxicity
in rats
AB - The drug
3,4-methylenedioxymethamphetamine (MDMA) is a serotonergic neurotoxicant that
causes hyperthermia and depletion of serotonin (5- HT) and
5-hydroxy-indole-3-acetic acid (5-HIAA) in the central nervous system. Formation
of neurotoxic metabolites of MDMA, e.g., 2,4,5- trihydroxy-methamphetamine and
2,4,5-trihydroxyamphetamine, involves hydroxyl and/or superoxide free radicals.
The present study was designed to determine whether the hydroxyl
free-radical-trapping agent salicylate could provide protection against MDMA
neurotoxicity in rats. In the acute studies, sodium salicylate (12.5-400 mg/kg,
calculated as free acid) was injected interperitoneally (i.p.) 1 h before
subcutaneous (s.c.) injections of MDMA (20 mg/kg as base). In the chronic
studies, sodium salicylate (3.1-100 mg/kg) was injected i.p. 1 h before
repeated s.c. injections of MDMA (10 mg/kg as base, twice daily, at 0830 and
1730 h for 4 consecutive days). Repeated MDMA administration depleted contents
of 5-HT and 5-HIAA in the frontal cortex, hippocampus and striatum.
Coadministration of salicylate plus MDMA did not significantly alter
MDMA-induced depletion of 5-HT and 5- HIAA in these tissues. Thus, salicylate,
a hydroxyl free-radical- trapping agent, does not protect against MDMA-induced
hyperthermia and depletion of 5-HT and 5-HIAA. These observations suggest that
MDMA- induced neurotoxicity may occur mainly through the production of
superoxide or other radicals rather than hydroxyl free radicals. Salicylate
actually potentiated MDMA-induced hyperthermia and lethality, findings that
might be of clinical relevance
MH - Adrenergic
Uptake Inhibitors
MH - toxicity
MH - Animal
MH - Biogenic
Monoamines
MH - metabolism
MH - Body
Temperature
MH - drug effects
MH - Brain Chemistry
MH - Free Radical
Scavengers
MH - administration
& dosage
MH - pharmacology
MH - Hydroxyl
Radical
MH -
Injections,Intraperitoneal
MH - Male
MH -
N-Methyl-3,4-methylenedioxyamphetamine
MH - Nervous System
Diseases
MH - chemically
induced
MH - Rats
MH -
Rats,Sprague-Dawley
MH - Salicylic Acids
MH - Superoxides
RP - NOT IN FILE
NT - UI - 97469600LA
- EngRN - 0 (Adrenergic Uptake Inhibitors)RN - 0 (Biogenic Monoamines)RN - 0
(Free Radical Scavengers)RN - 0 (Salicylic Acids)RN - 11062-77-4
(Superoxides)RN - 3352-57-6 (Hydroxyl Radical)RN - 42542-10-9
(N-Methyl-3,4-methylenedioxyamphetamine)RN - 69-72-7 (Salicylic Acid)PT -
JOURNAL ARTICLEDA - 19980206IS - 0091-3057SB - MCY - UNITED STATESJC - P3QAA -
AuthorEM - 199804
UR - PM:0009329062
SO - Pharmacol
Biochem Behav 1997 Nov ;58(3):701-708
120
UI - 138
AU - Baker LE
AU - M