"目录号: HY-14539
GPCR/G ProteinNeuronal Signaling-
Clozapine (HF 1854) 是用于治疗精神分裂症的抗精神病药。氯氮平是多巴胺和许多其他受体的有效拮抗剂，结合M1受体的Ki值为9.5 nM。
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生物活性
Description
Clozapine (HF 1854) is an antipsychotic used to treat schizophrenia. Clozapine is a potent antagonist of dopamine and a number of other receptors, with aKiof 9.5 nM forM1receptor.
IC50& Target
Ki: 9.5 nM (M1), 51 nM (α2-adrenoceptor), 75 nM (D2)[1]
In Vitro
Clozapine shows the unique property of having antipsychotic action but no Parkinson-like motor side effects. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine is very potent at D2 receptor with a Kiof 75 nM. Clozapine is also potent at the α2-adrenoceptor with a Kivalue of 51 nM[1]. Clozapine causes paradoxical downregulation of 5-HT2Areceptors. Clozapine also binds to 5-HT6and 5-HT7receptors with high affnity[2].
In Vivo
Head-twitch response is decreased and [3H]ketanserin binding is downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2AmRNA is reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, is rescued 7 days after chronicclozapine[3].
Clinical Trial
Anders Fink-Jensen, MD, DMSci-University of Copenhagen-Rigshospitalet, Denmark-Psychiatric Centre Rigshospitalet
Schizophrenia
September 2015
Phase 4
Tirat Carmel Mental Health Center-Technion, Israel Institute of Technology-Ben-Gurion University of the Negev-Beersheva Mental Health Center-Sha’ar Menashe Mental Health Center-HaEmek Medical Center, Israel-The Nazareth Hospital, Israel
Schizophrenia
October 2012
Phase 4
Northwell Health-National Institute of Mental Health (NIMH)
Schizophrenia
December 2000
Phase 1-Phase 2
University of British Columbia
Psychotic Disorders-Schizophrenia
January 2015
Phase 4
Centre for Addiction and Mental Health-Canadian Institutes of Health Research (CIHR)
Schizophrenia
April 2016
Dartmouth-Hitchcock Medical Center-National Institute on Drug Abuse (NIDA)-University of Missouri, Kansas City-VA Medical Center-West Los Angeles-University of South Carolina
Schizophrenia-Dual Diagnosis-Schizoaffective Disorder-Psychotic Disorder-Cannabis Abuse
October 2000
Phase 4
Centre for Addiction and Mental Health
Schizophrenia-Schizoaffective Disorder
August 2016
Phase 4
Novartis
Schizophrenia
November 2005
Phase 3
Harvard Medical School-National Institute of Mental Health (NIMH)-Dartmouth-Hitchcock Medical Center-Commonwealth Research Center, Massachusetts-Novartis
Schizophrenia
March 1996
Phase 4
Novartis
Schizophrenia
April 2001
Phase 2
Dartmouth-Hitchcock Medical Center-University of South Carolina-Michigan State University-University of Miami-University of Massachusetts, Worcester
Schizophrenia-Cannabis Abuse-Cannabis Dependence-Dual Diagnosis
April 2013
Phase 4
Harvard Medical School-National Institute of Mental Health (NIMH)-Dartmouth-Hitchcock Medical Center-Commonwealth Research Center, Massachusetts-Eli Lilly and Company
Schizophrenia
August 1998
Phase 4
Seoul National University Bundang Hospital
Schizophrenia-Schizoaffective Disorder
July 2011
Khon Kaen University
Schizophrenia
June 2008
Taipei Medical University Hospital-National Health Research Institutes, Taiwan
Schizophrenia
January 2008
Phase 4
Dartmouth-Hitchcock Medical Center-National Institute of Mental Health (NIMH)
Cannabis-Related Disorder-Substance-Related Disorders-Schizophrenia-Psychotic Disorders
June 2006
Geha Mental Health Center
Schizophrenia-Treatment Resistant Disorders
October 2011
Universidad Nacional de Rosario
Schizophrenia-Schizophrenic Disorders-Psychotic Disorder
January 2009
Phase 4
Indiana University School of Medicine-Hoffmann-La Roche-Shekhar, Anantha M.D., Ph.D.-Indiana University
Schizophrenia
September 2005
Phase 3
University of Maryland
Schizophrenia
July 2015
Dartmouth-Hitchcock Medical Center-National Institute on Alcohol Abuse and Alcoholism (NIAAA)-Harvard Medical School-Commonwealth Research Center, Massachusetts-Novartis
Schizophrenia-Dual Diagnosis-Schizoaffective Disorder-Psychotic Disorder-Substance Abuse-Alcohol Abuse
May 1999
Phase 4
Hospital de Clinicas de Porto Alegre-Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.-Conselho Nacional de Desenvolvimento Científico e Tecnológico
Bipolar Disorder
October 2015
Phase 4
Nathan Kline Institute for Psychiatric Research
Schizophrenia
June 1999
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Bipolar Disorder
May 2002
Phase 3
Centre for Addiction and Mental Health-The Ian Douglas Bebensee Foundation
Schizophrenia-Schizoaffective Disorder
May 1999
Phase 4
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Bipolar Disorder
January 2002
Phase 2
Harvard Medical School-National Institute of Mental Health (NIMH)-Dartmouth-Hitchcock Medical Center-Commonwealth Research Center, Massachusetts-Novartis
Schizophrenia
December 1994
Phase 4
Beersheva Mental Health Center
Schizophrenia
Phase 3
Azur Pharma, Inc
Weight Gain-Sialorrhea
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Childhood Schizophrenia-Psychotic Disorder-Schizophrenia
June 1997
Phase 4
Pfizer
Schizophrenia
January 2003
Phase 3
Taipei Medical University WanFang Hospital-Taipei City Hospital
Metabolic Syndrome
May 2013
Phase 4
Vanderbilt University
Schizophrenia-Schizoaffective Disorder
May 2000
Memorial Hospital of Rhode Island-FDA Office of Orphan Products Development
Parkinson Disease
October 1993
Massachusetts General Hospital
Schizophrenia
March 1998
Phase 3
Northwell Health-National Institute of Mental Health (NIMH)
Schizophrenia
October 2001
Phase 4
University of Massachusetts, Worcester-National Institutes of Health (NIH)
Schizophrenia-Schizoaffective Disorder
March 2009
Phase 4
Central South University-Shanghai Mental Health Center-Sichuan University-Capital Medical University-Nanjing Medical University-Jiangxi Mental Hospital-Hunan Mental Hospital-Guangzhou Mental Hospital-Chongqing Metal Institute-Henan Mental Hospital
Schizophrenia
February 2005
Phase 4
Centre for Addiction and Mental Health-Canadian Psychiatric Research Foundation
Schizophrenia
November 2006
Shanghai Mental Health Center
Schizophrenia
November 2016
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Panic Disorder
February 2002
Phase 4
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Mental Retardation-Developmental Delay Disorder
July 1998
Phase 3
Rene Kahn-King's College London-Technische Universität München-University of Manchester-Ludwig-Maximilians - University of Munich-UMC Utrecht
Schizophrenia-Schizophreniform Disorder-Schizoaffective Disorder
May 2011
Phase 4
National Institute of Mental Health (NIMH)
