1
UI  - 1
AU  - Drake RE
AU  - Xie H
AU  - McHugo GJ
AU  - Green AI
AD  - New Hampshire-Dartmouth Psychiatric Research Center, Dartmouth Medical School, Lebanon, NH, USA. Robert.E.Drake@Dartmouth.edu
TI  - The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia [In Process Citation]
AB  - Several case studies indicate that clozapine use is associated with reductions in the use of nicotine, alcohol, or illicit drugs. Although not designed to assess clozapine, this study explored a posteriori the effects of clozapine on alcohol and drug use disorders among schizophrenia patients. Among 151 patients with schizophrenia or schizoaffective disorder and co-occurring substance use disorder who were studied in a dual-disorder treatment program, 36 received clozapine during the study for standard clinical indications. All participants were assessed prospectively at baseline and every 6 months over 3 years for psychiatric symptoms and substance use. Alcohol- abusing patients taking clozapine experienced significant reductions in severity of alcohol abuse and days of alcohol use while on clozapine. For example, they averaged 54.1 drinking days during 6-month intervals while off clozapine and 12.5 drinking days while on clozapine. They also improved more than patients who did not receive clozapine. At the end of the study, 79.0 percent of the patients on clozapine were in remission from alcohol use disorder for 6 months or longer, while only 33.7 percent of those not taking clozapine were remitted. Findings related to other drugs in relation to clozapine were also positive but less clear because of the small number of patients with drug use disorders. This study was limited by the naturalistic design and the lack of prospective, standardized measures of clozapine use. The use of clozapine by patients with co-occurring substance disorders deserves further study in randomized clinical trials
RP  - NOT IN FILE
NT  - UI - 20340151LA - EngID - MH-46072/MH/NIMHID - MH-47567/MH/NIMHID - MH-00839/MH/NIMHID - +DA - 20000706IS - 0586-7614SB - MCY - UNITED STATESJC - UDHAA - AUTHORRO - O:099
UR  - PM:0010885642
SO  - Schizophr Bull 2000  ;26(2):441-449

2
UI  - 2
AU  - Kameda G
AU  - Dadmarz M
AU  - Vogel WH
AD  - Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
TI  - Influence of various drugs on the voluntary intake of nicotine by rats
AB  - The effects of the dopaminergic agonists (L-dopa, pergolide) and antagonists (haloperidol, clozapin) and a cholinergic agonist (tacrine) and antagonist (mecamylamine) on the voluntary intake of nicotine were investigated with the 2-bottle paradigm with the test drugs being dissolved directly in the drinking fluid of the animals. This method was found to be a reliable procedure to quickly screen compounds with specific sites of action in the brain for their effects on the voluntary intake of nicotine or perhaps other substances of abuse as well. L-dopa, pergolide and haloperidol did not affect the intake of nicotine, whereas tacrine increased it slightly and clozapine and mecamylamine markedly. These results indicate that blockade of nicotinic and dopaminergic D4 receptors partially reduce the desired effect of nicotine by forcing the animals to consume more of this substance. Copyright 2000 S. Karger AG, Basel
MH  - Administration,Oral
MH  - Animal
MH  - Behavior,Animal
MH  - drug effects
MH  - Choice Behavior
MH  - Cholinesterase Inhibitors
MH  - administration & dosage
MH  - Dopamine Agents
MH  - Dopamine Agonists
MH  - Dopamine Antagonists
MH  - Drinking Behavior
MH  - Drug Antagonism
MH  - Drug Synergism
MH  - GABA Antagonists
MH  - Male
MH  - Nicotine
MH  - Nicotinic Agonists
MH  - Nicotinic Antagonists
MH  - Rats
MH  - Rats,Sprague-Dawley
MH  - Receptors,Dopamine D2
MH  - antagonists & inhibitors
MH  - Self Administration
MH  - Serotonin Antagonists
RP  - NOT IN FILE
NT  - UI - 20291245LA - EngRN - 0 (Cholinesterase Inhibitors)RN - 0 (Dopamine Agents)RN - 0 (Dopamine Agonists)RN - 0 (Dopamine Antagonists)RN - 0 (GABA Antagonists)RN - 0 (Nicotinic Agonists)RN - 0 (Nicotinic Antagonists)RN - 0 (Receptors, Dopamine D2)RN - 0 (Serotonin Antagonists)RN - 137750-34-6 (dopamine D4 receptor)RN - 54-11-5 (Nicotine)PT - JOURNAL ARTICLEDA - 20000906IS - 0302-282XSB - MCY - SWITZERLANDJC - NZMAA - AuthorEM - 200011
UR  - PM:0010828730
SO  - Neuropsychobiology 2000  ;41(4):205-209

3
UI  - 3
AU  - Lyon ER
AD  - G. Pierce Wood Memorial Hospital, Arcadia, Florida 34266-9627, USA. edward-lyon@dcf.state.fl.us
TI  - A review of the effects of nicotine on schizophrenia and antipsychotic medications
AB  - OBJECTIVE: Research on the impact of nicotine on schizophrenia and antipsychotic medications was reviewed to determine ways to improve treatment planning for patients with schizophrenia who smoke and to evaluate smoking cessation programs for this population. METHODS: All major research databases were searched. The review focuses on reports published since 1990. RESULTS: Smoking improves processing of auditory stimuli (sensory gating) by patients with schizophrenia and may lessen negative symptoms by increasing dopamine in the nucleus accumbens and the prefrontal and frontal cortex. Use of traditional antipsychotics may result in patients' smoking more, whereas patients taking atypical antipsychotics may smoke less. Patients who smoke metabolize antipsychotics faster than nonsmoking patients. Smoking cessation programs for outpatients with schizophrenia report a success rate of about 12 percent after six months. No studies of cessation programs for chronically ill inpatients with schizophrenia have been published. Several hospitals have implemented smoking bans with equivocal results. CONCLUSIONS: Nicotine affects both schizophrenia and antipsychotic medications. Neurobiological and psychosocial factors reinforce the high use of nicotine by patients with schizophrenia
MH  - Antipsychotic Agents
MH  - metabolism
MH  - therapeutic use
MH  - Auditory Perception
MH  - drug effects
MH  - Chlorpromazine
MH  - Chronic Disease
MH  - Clozapine
MH  - Databases
MH  - Dopamine
MH  - Dose-Response Relationship,Drug
MH  - Frontal Lobe
MH  - Human
MH  - Nicotine
MH  - pharmacology
MH  - Nucleus Accumbens
MH  - Prefrontal Cortex
MH  - Schizophrenia
MH  - diagnosis
MH  - drug therapy
MH  - Severity of Illness Index
MH  - Smoking Cessation
RP  - NOT IN FILE
NT  - UI - 99436553LA - EngRN - 0 (Antipsychotic Agents)RN - 50-53-3 (Chlorpromazine)RN - 51-61-6 (Dopamine)RN - 54-11-5 (Nicotine)RN - 5786-21-0 (Clozapine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19991230IS - 1075-2730SB - MCY - UNITED STATESJC - B8TAA - AuthorEM - 200003
UR  - PM:0010506305
SO  - Psychiatr Serv 1999 Oct ;50(10):1346-1350

4
UI  - 4
AU  - McEvoy JP
AU  - Freudenreich O
AU  - Wilson WH
AD  - Duke University Medical Center, Durham, NC, USA
TI  - Smoking and therapeutic response to clozapine in patients with schizophrenia
AB  - BACKGROUND: Of patients with schizophrenia, 70 to 80% smoke. Nicotine corrects certain information processing and cognitive psychomotor deficits seen in many patients with schizophrenia. Clozapine, but not conventional antipsychotics, has been shown to correct some of these deficits. METHODS: We assessed psychopathology and smoking in 70 patients with treatment refractory schizophrenia (55 smokers and 15 nonsmokers) at baseline when they were receiving conventional antipsychotics and again after they were switched to clozapine. RESULTS: Smokers showed significantly greater therapeutic response to clozapine than nonsmokers. Smokers smoked less when treated with clozapine than when treated with conventional antipsychotics. CONCLUSIONS: Certain patients with schizophrenia have contributing pathophysiologic mechanisms that respond favorably to either nicotine or clozapine
MH  - Adult
MH  - Antipsychotic Agents
MH  - therapeutic use
MH  - Brief Psychiatric Rating Scale
MH  - Clozapine
MH  - metabolism
MH  - Dose-Response Relationship,Drug
MH  - Female
MH  - Human
MH  - Male
MH  - Middle Age
MH  - Nicotine
MH  - pharmacology
MH  - Reference Values
MH  - Schizophrenia
MH  - diagnosis
MH  - drug therapy
MH  - Smoking
MH  - psychology
MH  - Support,Non-U.S.Gov't
MH  - Support,U.S.Gov't,P.H.S.
MH  - Treatment Outcome
RP  - NOT IN FILE
NT  - UI - 99322786LA - EngRN - 0 (Antipsychotic Agents)RN - 54-11-5 (Nicotine)RN - 5786-21-0 (Clozapine)PT - JOURNAL ARTICLEID - NIDA 08434DA - 19991220IS - 0006-3223SB - MCY - UNITED STATESJC - A3SAA - AuthorEM - 200002
UR  - PM:0010394482
SO  - Biol Psychiatry 1999 Jul 1 ;46(1):125-129

5
UI  - 5
AU  - Ufer M
AU  - Dadmarz M
AU  - Vogel WH
AD  - Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia PA, USA
TI  - Voluntary consumption of amphetamine, cocaine, ethanol and morphine by rats as influenced by a preceding period of forced drug intake and clozapine
AB  - Forced nicotine intake was previously found to decrease a subsequent free choice selection, whereas clozapine (CL) caused a marked increase in its consumption. Here these findings are extended to ethanol, cocaine, morphine and amphetamine. Forced intake of ethanol, cocaine, morphine and amphetamine had no major effect on a subsequent voluntary intake. CL, a dopamine D4 antagonist, increased the voluntary consumption of amphetamine and morphine with no effects on ethanol or cocaine intake. Only for cocaine was it found that low-consuming rats increased but high-consuming rats decreased their voluntary cocaine intake by CL. Thus, forced drug exposure per se does not lead to subsequent enhancement of voluntary intake; CL exerts differential effects on intake of these drugs, and a specific dopaminergic set point may govern the voluntary intake of cocaine by individual rats
MH  - Administration,Oral
MH  - Amphetamine
MH  - administration & dosage
MH  - pharmacology
MH  - Animal
MH  - Central Nervous System Depressants
MH  - Clozapine
MH  - Cocaine
MH  - Comparative Study
MH  - Dopamine Agents
MH  - Ethanol
MH  - Male
MH  - Morphine
MH  - Narcotics
MH  - Rats
MH  - Rats,Sprague-Dawley
MH  - Self Administration
MH  - Substance-Related Disorders
MH  - etiology
RP  - NOT IN FILE
NT  - UI - 99263074LA - EngRN - 0 (Central Nervous System Depressants)RN - 0 (Dopamine Agents)RN - 0 (Narcotics)RN - 300-62-9 (Amphetamine)RN - 50-36-2 (Cocaine)RN - 57-27-2 (Morphine)RN - 5786-21-0 (Clozapine)RN - 64-17-5 (Ethanol)PT - JOURNAL ARTICLEDA - 19990622IS - 0031-7012SB - MCY - SWITZERLANDJC - P43AA - AuthorEM - 199908
UR  - PM:0010325573
SO  - Pharmacology 1999 Jun ;58(6):285-291

6
UI  - 6
AU  - Chatterton R
AU  - Sanderson L
AU  - Van Leent S
AU  - Plant K
TI  - Does clozapine affect smoking rates? [letter]
MH  - Clozapine
MH  - pharmacokinetics
MH  - therapeutic use
MH  - Drug Interactions
MH  - Human
MH  - Nicotine
MH  - Psychiatric Status Rating Scales
MH  - Schizophrenia
MH  - diagnosis
MH  - drug therapy
MH  - Schizophrenic Psychology
MH  - Smoking
MH  - prevention & control
MH  - psychology
RP  - NOT IN FILE
NT  - UI - 99181851LA - EngRN - 54-11-5 (Nicotine)RN - 5786-21-0 (Clozapine)PT - LETTERDA - 19990427IS - 0004-8674SB - MCY - AUSTRALIAJC - 9I6EM - 199907
UR  - PM:0010084360
SO  - Aust N Z J Psychiatry 1998 Dec ;32(6):890-891

7
UI  - 7
AU  - Oyewumi LK
TI  - Smoking cessation and clozapine side effects [letter]
MH  - Antipsychotic Agents
MH  - administration & dosage
MH  - adverse effects
MH  - Case Report
MH  - Clozapine
MH  - Drug Interactions
MH  - Human
MH  - Male
MH  - Middle Age
MH  - Nicotine
MH  - pharmacology
MH  - Nicotinic Agonists
MH  - Schizophrenia
MH  - drug therapy
MH  - Smoking Cessation
RP  - NOT IN FILE
NT  - UI - 98446404LA - EngRN - 0 (Antipsychotic Agents)RN - 0 (Nicotinic Agonists)RN - 54-11-5 (Nicotine)RN - 5786-21-0 (Clozapine)PT - LETTERDA - 19990322IS - 0706-7437SB - MCY - CANADAJC - CLREM - 199905
UR  - PM:0009773227
SO  - Can J Psychiatry 1998 Sep ;43(7):748

8
UI  - 8
AU  - Buckley PF
AD  - Department of Psychiatry, Case Western Reserve University, and the Northcoast Behavioral Healthcare System, Cleveland, Ohio 44106, USA
TI  - Substance abuse in schizophrenia: a review
AB  - Approximately half of the patients who suffer from schizophrenia are also substance abusers at some time during their illness. The motivational drive toward abusive consumption is compounded in individuals with schizophrenia who turn toward substances with reinforcing properties to alleviate aspects of psychosis. This review examines the prevalence, etiology, and clinical effects of substance abuse (e.g., alcohol, nicotine, cocaine) among individuals with schizophrenia. Clearly, substance abuse persists despite and in spite of treatment with typical antipsychotics. The efficacy of newer generation antipsychotics in the reduction of substance abuse among the schizophrenic population has yet to be established, but clozapine has been shown to reduce alcohol, smoking, and cocaine use. Hence, clozapine is a therapeutic option for dually diagnosed patients because of its superior efficacy relative to conventional neuroleptics and its capacity to control substance abuse
MH  - Antipsychotic Agents
MH  - pharmacology
MH  - therapeutic use
MH  - Clozapine
MH  - Comorbidity
MH  - Cost-Benefit Analysis
MH  - Diagnosis,Dual (Psychiatry)
MH  - Drug Monitoring
MH  - Human
MH  - Precipitating Factors
MH  - Prevalence
MH  - Schizophrenia
MH  - diagnosis
MH  - drug therapy
MH  - epidemiology
MH  - Substance-Related Disorders
MH  - Support,Non-U.S.Gov't
RP  - NOT IN FILE
NT  - UI - 98200406LA - EngRN - 0 (Antipsychotic Agents)RN - 5786-21-0 (Clozapine)PT - JOURNAL ARTICLEPT - REVIEWPT - REVIEW, TUTORIALDA - 19980410IS - 0160-6689SB - MCY - UNITED STATESJC - HICAA - AuthorEM - 199806
UR  - PM:0009541335
SO  - J Clin Psychiatry 1998  ;59 Suppl 3():26-30

9
UI  - 9
AU  - Brioni JD
AU  - Kim DJ
AU  - O'Neill AB
AU  - Williams JE
AU  - Decker MW
AD  - Pharmaceutical Products Division, Abbott Laboratories, IL 60064-3500
TI  - Clozapine attenuates the discriminative stimulus properties of (-)- nicotine
AB  - Rats were trained to discriminate 1.9 mumol/kg (-)-nicotine (0.3 mg/kg) from saline in a standard two-bar operant conditioning paradigm with food reinforcement. The effect of neuronal nicotinic acetylcholine receptor (nAChR) agonists and antagonists were verified, and the participation of dopaminergic receptors subtypes in the expression of the (-)-nicotine cue was investigated with cis-flupentixol (D1-D2 antagonist), haloperidol (D2 antagonist) and clozapine (D4 antagonist). The stereoselectivity of the behavioral response was indicated by the 10-fold less sensitivity to (+)-nicotine in (-)-nicotine-trained rats. (+/-)-Anabasine and (-)-cytisine exhibited partial agonist profiles at the 1.9 mumol/kg dose while (-)-lobeline was devoid of any effect in doses up to 19 mumol/kg. (-)-Lobeline did not show antagonist properties in this paradigm. The nicotinic channel blockers mecamylamine, chlorisondamine and hexamethonium were inactive on their own but mecamylamine and chlorisondamine were able to block the effect of (-)-nicotine. Clozapine attenuated the (-)-nicotine cue while cis- flupentixol and haloperidol were ineffective. Similar doses of cis- flupentixol significantly blocked the locomotor stimulant effect of (-)- nicotine in rats indicating that blockade of dopaminergic receptors was achieved at the doses used in the drug discrimination studies. These data suggest that the discriminative stimulus properties of (-)- nicotine are mediated through neuronal nAChRs and involves the activation of dopaminergic receptors of the D4 subtype
MH  - Alkaloids
MH  - pharmacology
MH  - Anabasine
MH  - Animal
MH  - Chlorisondamine
MH  - Clozapine
MH  - Comparative Study
MH  - Conditioning,Operant
MH  - drug effects
MH  - Discrimination (Psychology)
MH  - Dose-Response Relationship,Drug
MH  - Flupenthixol
MH  - Lobeline
MH  - Male
MH  - Motor Activity
MH  - Nicotine
MH  - antagonists & inhibitors
MH  - Rats
MH  - Rats,Wistar
MH  - Stereoisomerism
RP  - NOT IN FILE
NT  - UI - 94306152LA - EngRN - 0 (Alkaloids)RN - 2709-56-0 (Flupenthixol)RN - 485-35-8 (cytisine)RN - 494-52-0 (Anabasine)RN - 54-11-5 (Nicotine)RN - 5786-21-0 (Clozapine)RN - 69-27-2 (Chlorisondamine)RN - 90-69-7 (Lobeline)PT - JOURNAL ARTICLEDA - 19940812IS - 0006-8993SB - MCY - NETHERLANDSJC - B5LAA - AuthorEM - 199410
UR  - PM:0008032906
SO  - Brain Res 1994 Apr 18 ;643(1-2):1-9

10
UI  - 10
AU  - Kiba H
AU  - Jayaraman A
AD  - Department of Neurology, LSU School of Medicine, New Orleans 70112
TI  - Nicotine induced c-fos expression in the striatum is mediated mostly by dopamine D1 receptor and is dependent on NMDA stimulation
AB  - The powerful psychostimulant and positive reinforcing effects of nicotine have been speculated to be mediated by the dopaminergic neurons of the ventral tegemental area (VTA) and their terminals in the nucleus accumbens. To extend our understanding of nicotine and dopamine interactions, we mapped the pattern of c-fos expression in the striatum as an important marker of some of the earliest changes that occur at gene transcription level. Acute nicotine injections in rats led to Fos expression more prominently in the caudatoputamen than in the nucleus accumbens in a dose-dependent fashion. Fos-reactive cells were more prominent in the central and dorsomedial limbic caudatoputamen than in the dorsolateral sensory-motor striatum. Injections of mecamylamine completely blocked nicotine-induced Fos expression. Injections of the selective dopamine D1 antagonist SCH 23390, but not D2 antagonist YM 09151-2 or Clozapine, a drug with high affinity to D4 receptors, before nicotine injections, completely blocked Fos expression in the striatum. Nicotine induced Fos expression was also blocked completely by the NMDA receptor antagonists MK-801 and CPP. These results suggest that nicotine-induced Fos expression in the striatum is mediated mostly by dopamine D1 receptors and that the Fos expression is also dependent on N-methyl-D-aspartate (NMDA) stimulation
MH  - Animal
MH  - Benzamides
MH  - pharmacology
MH  - Clozapine
MH  - Corpus Striatum
MH  - drug effects
MH  - metabolism
MH  - Dizocilpine Maleate
MH  - Gene Expression Regulation
MH  - Genes,fos
MH  - Glutamates
MH  - physiology
MH  - Male
MH  - Mecamylamine
MH  - Nicotine
MH  - Nucleus Accumbens
MH  - Piperazines
MH  - Proto-Oncogene Proteins c-fos
MH  - biosynthesis
MH  - Rats
MH  - Rats,Sprague-Dawley
MH  - Receptors,Dopamine
MH  - Receptors,N-Methyl-D-Aspartate
MH  - Reward
MH  - Sch-23390
MH  - Support,Non-U.S.Gov't
RP  - NOT IN FILE
NT  - UI - 94301175LA - EngRN - 0 (Benzamides)RN - 0 (Glutamates)RN - 0 (Piperazines)RN - 0 (Proto-Oncogene Proteins c-fos)RN - 0 (Receptors, Dopamine)RN - 0 (Receptors, N-Methyl-D-Aspartate)RN - 100828-16-8 (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid)RN - 54-11-5 (Nicotine)RN - 56-86-0 (Glutamic Acid)RN - 5786-21-0 (Clozapine)RN - 60-40-2 (Mecamylamine)RN - 70325-83-6 (nemonapride)RN - 77086-22-7 (Dizocilpine Maleate)RN - 87075-17-0 (Sch-23390)PT - JOURNAL ARTICLEDA - 19940808IS - 0169-328XSB - MCY - NETHERLANDSJC - MBRAA - AuthorEM - 199410
UR  - PM:0007913201
SO  - Brain Res Mol Brain Res 1994 Apr ;23(1-2):1-13