"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。
Dopamine Receptor
相关产品
Chlorpromazine hydrochloride-Brexpiprazole-Haloperidol-Cabergoline-Cariprazine hydrochloride-L-DOPA-Perphenazine-Dopamine hydrochloride-Oxidopamine hydrobromide-Sertindole-B-HT 920-Azaperone-Fluphenazine dihydrochloride-Iloperidone-Sumanirole maleate-
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
NCT02625103
Anders Fink-Jensen, MD, DMSci-University of Copenhagen-Rigshospitalet, Denmark-Psychiatric Centre Rigshospitalet
Schizophrenia
September 2015
Phase 4
NCT01663077
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
NCT00042224
Northwell Health-National Institute of Mental Health (NIMH)
Schizophrenia
December 2000
Phase 1-Phase 2
NCT02286206
University of British Columbia
Psychotic Disorders-Schizophrenia
January 2015
Phase 4
NCT02714894
Centre for Addiction and Mental Health-Canadian Institutes of Health Research (CIHR)
Schizophrenia
April 2016
NCT00498550
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
NCT02639702
Centre for Addiction and Mental Health
Schizophrenia-Schizoaffective Disorder
August 2016
Phase 4
NCT00250575
Novartis
Schizophrenia
November 2005
Phase 3
NCT00169091
Harvard Medical School-National Institute of Mental Health (NIMH)-Dartmouth-Hitchcock Medical Center-Commonwealth Research Center, Massachusetts-Novartis
Schizophrenia
March 1996
Phase 4
NCT00154258
Novartis
Schizophrenia
April 2001
Phase 2
NCT01639872
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
NCT00169065
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
NCT01398189
Seoul National University Bundang Hospital
Schizophrenia-Schizoaffective Disorder
July 2011
NCT00753051
Khon Kaen University
Schizophrenia
June 2008
NCT01401491
Taipei Medical University Hospital-National Health Research Institutes, Taiwan
Schizophrenia
January 2008
Phase 4
NCT00573287
Dartmouth-Hitchcock Medical Center-National Institute of Mental Health (NIMH)
Cannabis-Related Disorder-Substance-Related Disorders-Schizophrenia-Psychotic Disorders
June 2006
NCT01448499
Geha Mental Health Center
Schizophrenia-Treatment Resistant Disorders
October 2011
NCT01279213
Universidad Nacional de Rosario
Schizophrenia-Schizophrenic Disorders-Psychotic Disorder
January 2009
Phase 4
NCT00216281
Indiana University School of Medicine-Hoffmann-La Roche-Shekhar, Anantha M.D., Ph.D.-Indiana University
Schizophrenia
September 2005
Phase 3
NCT02404155
University of Maryland
Schizophrenia
July 2015
NCT00169026
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
NCT02562287
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
NCT01123408
Nathan Kline Institute for Psychiatric Research
Schizophrenia
June 1999
NCT00036582
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Bipolar Disorder
May 2002
Phase 3
NCT02640300
Centre for Addiction and Mental Health-The Ian Douglas Bebensee Foundation
Schizophrenia-Schizoaffective Disorder
May 1999
Phase 4
NCT00029458
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Bipolar Disorder
January 2002
Phase 2
NCT00169039
Harvard Medical School-National Institute of Mental Health (NIMH)-Dartmouth-Hitchcock Medical Center-Commonwealth Research Center, Massachusetts-Novartis
Schizophrenia
December 1994
Phase 4
NCT00189995
Beersheva Mental Health Center
Schizophrenia
Phase 3
NCT00683891
Azur Pharma, Inc
Weight Gain-Sialorrhea
NCT00001656
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Childhood Schizophrenia-Psychotic Disorder-Schizophrenia
June 1997
Phase 4
NCT00649844
Pfizer
Schizophrenia
January 2003
Phase 3
NCT02751307
Taipei Medical University WanFang Hospital-Taipei City Hospital
Metabolic Syndrome
May 2013
Phase 4
NCT00179231
Vanderbilt University
Schizophrenia-Schizoaffective Disorder
May 2000
NCT00004826
Memorial Hospital of Rhode Island-FDA Office of Orphan Products Development
Parkinson Disease
October 1993
NCT00000372
Massachusetts General Hospital
Schizophrenia
March 1998
Phase 3
NCT00048828
Northwell Health-National Institute of Mental Health (NIMH)
Schizophrenia
October 2001
Phase 4
NCT00981526
University of Massachusetts, Worcester-National Institutes of Health (NIH)
Schizophrenia-Schizoaffective Disorder
March 2009
Phase 4
NCT00654576
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
NCT00493233
Centre for Addiction and Mental Health-Canadian Psychiatric Research Foundation
Schizophrenia
November 2006
NCT02926976
Shanghai Mental Health Center
Schizophrenia
November 2016
NCT00031317
National Institute of Mental Health (NIMH)-National Institutes of Health Clinical Center (CC)
Panic Disorder
February 2002
Phase 4
NCT00065273
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Mental Retardation-Developmental Delay Disorder
July 1998
Phase 3
NCT01248195
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
NCT00014001
National Institute of Mental Health (NIMH)