DGIdb - CLOZAPINE Drug Record

CLOZAPINE chembl:CHEMBL42 Approved

Alternate Names:

CLOZAPINE RESOLUTION MIXTURE
HF-1854
CLOZARIL
FAZACLO
VERSACLOZ
ZAPONEX
CLOZAPINE
FAZACLO ODT
CLOZAPIN
CLOZAPINUM
CLORAZIL®
LEX123
CLOZAPINA
rxcui:2626
drugbank:00363
chembl:CHEMBL42
chemidplus:5786-21-0
pubchem.compound:2818

Drug Info:

Drug Categories	gaba antagonists
FDA Approval	1989
Drug Class	small molecule
Drug Indications	Antipsychotic Agents
Drug Class	antipsychotic agents
Year of Approval	1989
Drug Categories	adrenergic alpha-1 receptor antagonists
Drug Categories	adrenergic alpha-antagonists
Drug Categories	adrenergic antagonists
Drug Categories	agents producing tachycardia
Drug Categories	agents that produce hypertension
Drug Categories	agents that reduce seizure threshold
Drug Categories	anticholinergic agents
Drug Categories	antidepressive agents
Drug Categories	cytochrome p-450 cyp1a2 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp2c19 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp2c19 inhibitors (weak)
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 inducers
Drug Categories	cytochrome p-450 cyp3a4 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp3a4 inhibitors
Drug Categories	cytochrome p-450 cyp3a4 inhibitors (moderate)
Drug Categories	cytochrome p-450 cyp3a4 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 enzyme inducers
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	dopamine antagonists
Drug Categories	dopamine d2 receptor antagonists
Drug Categories	drugs causing inadvertant photosensitivity
Drug Categories	drugs that are mainly renally excreted
Drug Categories	heterocyclic compounds, fused-ring
Drug Categories	histamine antagonists
Drug Categories	histamine h1 antagonists
Drug Categories	muscarinic antagonists
Drug Categories	neurotoxic agents
Drug Categories	p-glycoprotein substrates
Drug Categories	photosensitizing agents
Drug Categories	qtc prolonging agents
Drug Categories	serotonin 5-ht2 receptor antagonists
Drug Categories	serotonin receptor antagonists
Drug Categories	ugt1a4 substrates

(7 More Sources)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
Lipska et al., 2003, Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs., Eur. J. Neurosci.
Arranz MJ et al., 1998, Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response., Pharmacogenetics
Eum S et al., 2017, Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report., BMC Psychiatry
Sukasem C et al., 2016, Impact of Pharmacogenetic Markers of CYP2D6 and DRD2 on Prolactin Response in Risperidone-Treated Thai Children and Adolescents With Autism Spectrum Disorders., J Clin Psychopharmacol
López-Rodríguez R et al., 2013, Pharmacodynamic genetic variants related to antipsychotic adverse reactions in healthy volunteers., Pharmacogenomics
Roke Y et al., 2013, The effect of the Taq1A variant in the dopamine D₂ receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys., Pharmacogenet Genomics
Müller DJ et al., 2012, Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain., Pharmacogenomics J
Hong CJ et al., 2010, Dopamine receptor D2 gene is associated with weight gain in schizophrenic patients under long-term atypical antipsychotic treatment., Pharmacogenet Genomics
Zhang JP et al., 2010, D2 receptor genetic variation and clinical response to antipsychotic drug treatment: a meta-analysis., Am J Psychiatry
Yasui-Furukori N et al., 2008, Association between dopamine-related polymorphisms and plasma concentrations of prolactin during risperidone treatment in schizophrenic patients., Prog Neuropsychopharmacol Biol Psychiatry
Bakker PR et al., 2008, Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions., Mol Psychiatry
Alenius M et al., 2008, Gene polymorphism influencing treatment response in psychotic patients in a naturalistic setting., J Psychiatr Res
Zai CC et al., 2007, Meta-analysis of two dopamine D2 receptor gene polymorphisms with tardive dyskinesia in schizophrenia patients., Mol Psychiatry
Suzuki A et al., 2001, The -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region is associated with anxiolytic and antidepressive effects during treatment with dopamine antagonists in schizophrenic patients., Pharmacogenetics
Batra S, 1976, Unconjugated estradiol in the myometrium of pregnancy., Endocrinology
Ohara K et al., 1998, Functional polymorphism of -141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia., Psychiatry Res
Li T et al., 1998, Case-control, haplotype relative risk and transmission disequilibrium analysis of a dopamine D2 receptor functional promoter polymorphism in schizophrenia., Schizophr Res
Shen YC et al., 2009, Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients., J Psychiatr Res
Xing Q et al., 2007, The relationship between the therapeutic response to risperidone and the dopamine D2 receptor polymorphism in Chinese schizophrenia patients., Int J Neuropsychopharmacol
Lencz et al., 2006, DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients., Am J Psychiatry
Lerman C et al., 2006, Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials., Neuropsychopharmacology
Hwang R et al., 2005, Association study of 12 polymorphisms spanning the dopamine D(2) receptor gene and clozapine treatment response in two treatment refractory/intolerant populations., Psychopharmacology (Berl)
Wu et al., 2005, Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients., Neurosci. Lett.
Yamanouchi Y et al., 2003, Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone., Pharmacogenomics J
Li T et al., 2002, Allelic association analysis of the dopamine D2, D3, 5-HT2A, and GABA(A)gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects., Am J Med Genet
Young et al., 2004, Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele., Br J Psychiatry
Weizman et al., 2003, The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms., Eur. J. Pharmacol.
Green et al., 2002, Treatment of schizophrenia and comorbid substance use disorder., Curr Drug Targets CNS Neurol Disord
Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
Stonehouse et al., 2005, Bromocriptine and clozapine regulate dopamine 2 receptor gene expression in the mouse striatum., J. Mol. Neurosci.
Takano et al., 2006, Time course of dopamine D2 receptor occupancy by clozapine with medium and high plasma concentrations., Prog. Neuropsychopharmacol. Biol. Psychiatry
Tresadern G et al., 2011, Molecular properties affecting fast dissociation from the D2 receptor., Bioorg Med Chem
Schmitt et al., 2003, Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain., Neurosci. Lett.
Patel et al., 2003, Pharmacological and functional characterisation of dopamine D4 receptors in the rat retina., Neuropharmacology
Glatt et al., 2003, Schizophrenia is not associated with DRD4 48-base-pair-repeat length or individual alleles: results of a meta-analysis., Biol. Psychiatry
Zhao et al., 2005, Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine., Int. J. Neurosci.
Nakane et al., 2005, 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist., Neuropharmacology
Kuballa et al., Central effects of nafadotride, a dopamine D3 receptor antagonist, in rats. Comparison with haloperidol and clozapine., Pharmacol Rep
Hwang R et al., 2007, Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response., J Psychopharmacol
Tiwari AK et al., 2010, Association study of polymorphisms in cholecystokinin gene and its receptors with antipsychotic induced weight gain in schizophrenia patients., Prog Neuropsychopharmacol Biol Psychiatry
Piatkov I et al., 2017, CYP2C19*17 protects against metabolic complications of clozapine treatment., World J Biol Psychiatry
Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol
Leysen et al., 1994, Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity., J Clin Psychiatry
Roegge et al., 2007, Histamine H1 receptor involvement in prepulse inhibition and memory function: relevance for the antipsychotic actions of clozapine., Pharmacol. Biochem. Behav.
Kontkanen et al., 2002, Chronic antipsychotic drug treatment induces long-lasting expression of fos and jun family genes and activator protein 1 complex in the rat prefrontal cortex., Neuropsychopharmacology
Navailles et al., 2006, Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo., Biol. Psychiatry
Sodhi et al., 2005, A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts., Mol. Pharmacol.
Ma X et al., 2014, HTR2C polymorphisms, olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: a meta-analysis., Int J Psychiatry Clin Pract
Houston JP et al., 2012, Pharmacogenomic associations with weight gain in olanzapine treatment of patients without schizophrenia., J Clin Psychiatry
Sicard MN et al., 2010, Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis., Pharmacogenomics
Risselada AJ et al., 2012, Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics: a replication study., Pharmacogenomics J
Opgen-Rhein C et al., 2010, Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample., Pharmacogenomics
Godlewska BR et al., 2009, Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene., Pharmacogenomics J
Mulder H et al., 2009, HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia: a replication study., J Clin Psychopharmacol
Mulder H et al., 2007, The association between HTR2C gene polymorphisms and the metabolic syndrome in patients with schizophrenia., J Clin Psychopharmacol
Mulder H et al., 2007, The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study., Pharmacogenomics J
Roth et al., 1994, Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors., J. Pharmacol. Exp. Ther.
Lacivita E et al., 2012, Investigations on the 1-(2-biphenyl)piperazine motif: identification of new potent and selective ligands for the serotonin(7) (5-HT(7)) receptor with agonist or antagonist action in vitro or ex vivo., J Med Chem
Goldstein, 1999, Quetiapine fumarate (Seroquel): a new atypical antipsychotic., Drugs Today
Reist et al., 2004, Inter-relationships of intermediate phenotypes for serotonin function, impulsivity, and a 5-HT2A candidate allele: His452Tyr., Mol. Psychiatry
McDonald et al., 2003, Enhancement of latent inhibition by two 5-HT2A receptor antagonists only when given at both pre-exposure and conditioning., Psychopharmacology (Berl.)
Heiser et al., 2004, Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro., Prog. Neuropsychopharmacol. Biol. Psychiatry
Broderick et al., 2004, Clozapine and cocaine effects on dopamine and serotonin release in nucleus accumbens during psychostimulant behavior and withdrawal., Prog. Neuropsychopharmacol. Biol. Psychiatry
Travis et al., 1998, 5-HT2A receptor blockade in patients with schizophrenia treated with risperidone or clozapine. A SPET study using the novel 5-HT2A ligand 123I-5-I-R-91150., Br J Psychiatry
Arranz et al., 1996, Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine., Neurosci. Lett.
Salloum NC et al., 2014, Towards the clinical implementation of pharmacogenetics in bipolar disorder., BMC Med
Shao et al., 2006, Antipsychotic drugs cause glial cell line-derived neurotrophic factor secretion from C6 glioma cells., J Psychiatry Neurosci
Dettling M et al., 2001, Genetic determinants of clozapine-induced agranulocytosis: recent results of HLA subtyping in a non-jewish caucasian sample., Arch Gen Psychiatry
Hwang R et al., 2011, Gene-gene interaction analyses between NMDA receptor subunit and dopamine receptor gene variants and clozapine response., Pharmacogenomics
Hwang R et al., 2010, Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant., Pharmacogenomics J
Smits et al., 2006, Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives., J. Med. Chem.
Sugata et al., 2007, Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses., Immunology
Adachi et al., 2006, Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats., Eur. J. Pharmacol.
Bosia M et al., 2015, COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine., Pharmacogenomics
Chou et al., 2003, Occupancy of 5-HT1A receptors by clozapine in the primate brain: a PET study., Psychopharmacology (Berl.)
Newman-Tancredi et al., 2003, Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924., Naunyn Schmiedebergs Arch. Pharmacol.
Tomić et al., 2004, Pharmacological evaluation of selected arylpiperazines with atypical antipsychotic potential., Bioorg. Med. Chem. Lett.
Zahorodna et al., 2004, The influence of repeated administration of clozapine and haloperidol on the effects of the activation of 5-HT(1A), 5-HT(2) and 5-HT(4) receptors in rat frontal cortex., J. Physiol. Pharmacol.
Hagino et al., 2002, Effects of clozapine on the efflux of serotonin and dopamine in the rat brain: the role of 5-HT1A receptors., Can. J. Physiol. Pharmacol.
Valevski A et al., 1998, HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients., Eur J Immunogenet
Saito T et al., 2016, Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population., Biol Psychiatry
Lieberman JA et al., 1990, HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia., Arch Gen Psychiatry
Wittmann et al., 2005, Clozapine potentiation of N-methyl-D-aspartate receptor currents in the nucleus accumbens: role of NR2B and protein kinase A/Src kinases., J. Pharmacol. Exp. Ther.
Mitjans M et al., 2015, Hypothalamic-pituitary-adrenal system, neurotrophic factors and clozapine response: association with FKBP5 and NTRK2 genes., Pharmacogenet Genomics
Dragovic S et al., 2013, Characterization of human cytochrome P450s involved in the bioactivation of clozapine., Drug Metab Dispos
Chetty et al., 2007, CYP-mediated clozapine interactions: how predictable are they?, Curr. Drug Metab.
Nurmi EL et al., 2013, Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies., Transl Psychiatry
Monteleone P et al., 2010, Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain., J Clin Psychopharmacol
Tiwari AK et al., 2010, A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in Schizophrenia., Neuropsychopharmacology
Fernø et al., 2006, Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs., BMC Neurosci
Delacrétaz A et al., 2017, Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs., Gene
Brandl EJ et al., 2016, The role of the ITIH3 rs2535629 variant in antipsychotic response., Schizophr Res
Rajkumar AP et al., 2012, Outcome definitions and clinical predictors influence pharmacogenetic associations between HTR3A gene polymorphisms and response to clozapine in patients with schizophrenia., Psychopharmacology (Berl)
Souza RP et al., 2010, Influence of serotonin 3A and 3B receptor genes on clozapine treatment response in schizophrenia., Pharmacogenet Genomics
Xu M et al., 2010, Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia., Prog Neuropsychopharmacol Biol Psychiatry
Kang et al., 2004, The effects of clozapine on the GSK-3-mediated signaling pathway., FEBS Lett.
Brandl EJ et al., 2014, Genetic variation in the GCG and in the GLP1R genes and antipsychotic-induced weight gain., Pharmacogenomics
Dettling M et al., 2001, Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry., Pharmacogenetics
Szuster-Ciesielska et al., Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers., Arch. Immunol. Ther. Exp. (Warsz.)
Kobayashi et al., 2000, Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes., Br. J. Pharmacol.
Kao AC et al., 2014, Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances., J Psychiatr Res
Atmaca et al., 2003, Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics., J Clin Psychiatry
Porcelli S et al., 2016, PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study., Neuropsychobiology
Zhang JP et al., 2016, Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis., Schizophr Bull
Czerwensky F et al., 2013, MC4R rs489693: a clinical risk factor for second generation antipsychotic-related weight gain?, Int J Neuropsychopharmacol
Malhotra AK et al., 2012, Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain., Arch Gen Psychiatry
Chowdhury NI et al., 2013, Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene., Pharmacogenomics J
van der Weide K et al., 2017, Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population., Pharmacogenomics J
Kohlrausch FB et al., 2010, Influence of serotonin transporter gene polymorphisms on clozapine response in Brazilian schizophrenics., J Psychiatr Res
Lara et al., 2001, Chronic treatment with clozapine, but not haloperidol, increases striatal ecto-5'-nucleotidase activity in rats., Neuropsychobiology
Taylor DL et al., 2016, Genetic association analysis of N-methyl-D-aspartate receptor subunit gene GRIN2B and clinical response to clozapine., Hum Psychopharmacol
Lieberman et al., 1994, Predictors of response to clozapine., J Clin Psychiatry
Brandl EJ et al., 2013, Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain., Hum Psychopharmacol
Jaquenoud Sirot E et al., 2009, ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine., J Clin Psychopharmacol
Palma BB et al., 2010, Functional characterization of eight human cytochrome P450 1A2 gene variants by recombinant protein expression., Pharmacogenomics J
Bolla E et al., 2011, Are CYP1A21F and 1C associated with clozapine tolerability?: a preliminary investigation., Psychiatry Res
Kohlrausch FB et al., 2013, The CYP1A2 -163C>A polymorphism is associated with clozapine-induced generalized tonic-clonic seizures in Brazilian schizophrenia patients., Psychiatry Res
Lee ST et al., 2012, Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response., J Clin Psychopharmacol
Erickson-Ridout KK et al., 2012, Glucuronidation of the second-generation antipsychotic clozapine and its active metabolite N-desmethylclozapine. Potential importance of the UGT1A1 A(TA)₇TAA and UGT1A4 L48V polymorphisms., Pharmacogenet Genomics
Zhang C et al., 2017, Complement 3 and metabolic syndrome induced by clozapine: a cross-sectional study and retrospective cohort analysis., Pharmacogenomics J
Boerma JS et al., 2011, Application of CYP102A1M11H as a tool for the generation of protein adducts of reactive drug metabolites., Chem Res Toxicol

CLOZAPINE DRD1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Trial Name -

Publications:

Hwang R et al., 2007, Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response., J Psychopharmacol

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

CLOZAPINE HTR1F

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:
CLOZAPINE ADRA1D

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:
CLOZAPINE HTR2B

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:
CLOZAPINE HTR5A

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:
CLOZAPINE DRD5

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:
CLOZAPINE ADRA1A

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

CLOZAPINE DRD2

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

Specific Action of the Ligand Antagonist

Publications:

Lipska et al., 2003, Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs., Eur. J. Neurosci.

Arranz MJ et al., 1998, Lack of association between a polymorphism in the promoter region of the dopamine-2 receptor gene and clozapine response., Pharmacogenetics

Eum S et al., 2017, Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report., BMC Psychiatry

CLOZAPINE DRD4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Antagonist

Novel drug target Established target

Publications:

Patel et al., 2003, Pharmacological and functional characterisation of dopamine D4 receptors in the rat retina., Neuropharmacology

Glatt et al., 2003, Schizophrenia is not associated with DRD4 48-base-pair-repeat length or individual alleles: results of a meta-analysis., Biol. Psychiatry

Zhao et al., 2005, Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine., Int. J. Neurosci.

CLOZAPINE ADRA1B

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

CLOZAPINE HRH1

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Trial Name -

Publications:

Leysen et al., 1994, Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity., J Clin Psychiatry

Roegge et al., 2007, Histamine H1 receptor involvement in prepulse inhibition and memory function: relevance for the antipsychotic actions of clozapine., Pharmacol. Biochem. Behav.

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

CLOZAPINE HTR2C

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

Specific Action of the Ligand Inverse agonist

Publications:

Navailles et al., 2006, Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo., Biol. Psychiatry

Sodhi et al., 2005, A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts., Mol. Pharmacol.

Ma X et al., 2014, HTR2C polymorphisms, olanzapine-induced weight gain and antipsychotic-induced metabolic syndrome in schizophrenia patients: a meta-analysis., Int J Psychiatry Clin Pract

CLOZAPINE HTR7

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Inverse agonist

Publications:

Roth et al., 1994, Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors., J. Pharmacol. Exp. Ther.

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Lacivita E et al., 2012, Investigations on the 1-(2-biphenyl)piperazine motif: identification of new potent and selective ligands for the serotonin(7) (5-HT(7)) receptor with agonist or antagonist action in vitro or ex vivo., J Med Chem

CLOZAPINE HTR2A

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Inverse agonist

Endogenous Drug? False

Direct Interaction? True

Publications:

Leysen et al., 1994, Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity., J Clin Psychiatry

Goldstein, 1999, Quetiapine fumarate (Seroquel): a new atypical antipsychotic., Drugs Today

Reist et al., 2004, Inter-relationships of intermediate phenotypes for serotonin function, impulsivity, and a 5-HT2A candidate allele: His452Tyr., Mol. Psychiatry

CLOZAPINE DRD3

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Hwang R et al., 2011, Gene-gene interaction analyses between NMDA receptor subunit and dopamine receptor gene variants and clozapine response., Pharmacogenomics

Hwang R et al., 2010, Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant., Pharmacogenomics J

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

CLOZAPINE HRH4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Antagonist

Trial Name -

Publications:

Smits et al., 2006, Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives., J. Med. Chem.

Sugata et al., 2007, Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses., Immunology

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

CLOZAPINE HTR1A

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

Specific Action of the Ligand Full agonist

Publications:

Bosia M et al., 2015, COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine., Pharmacogenomics

Chou et al., 2003, Occupancy of 5-HT1A receptors by clozapine in the primate brain: a PET study., Psychopharmacology (Berl.)

Newman-Tancredi et al., 2003, Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924., Naunyn Schmiedebergs Arch. Pharmacol.

CLOZAPINE ADRA2A

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE CHRM5

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE CHRM1

Interaction Types & Directionality:

antagonist (inhibitory)

allosteric modulator

Interaction Info:

Specific Action of the Ligand Positive

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE CHRM4

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE HTR1D

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

CLOZAPINE HTR3A

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Rajkumar AP et al., 2012, Outcome definitions and clinical predictors influence pharmacogenetic associations between HTR3A gene polymorphisms and response to clozapine in patients with schizophrenia., Psychopharmacology (Berl)

Souza RP et al., 2010, Influence of serotonin 3A and 3B receptor genes on clozapine treatment response in schizophrenia., Pharmacogenet Genomics

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

CLOZAPINE HTR6

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Inverse agonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE ADRA2B

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE HTR1B

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE HTR1E

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Full agonist

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE CALY

Interaction Types & Directionality:

other/unknown

Interaction Info:

Publications:

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.
CLOZAPINE CHRM2

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE ADRA2C

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE CHRM3

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry
CLOZAPINE SLC1A1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Schmitt et al., 2003, Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain., Neurosci. Lett.

CLOZAPINE CCKBR

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Tiwari AK et al., 2010, Association study of polymorphisms in cholecystokinin gene and its receptors with antipsychotic induced weight gain in schizophrenia patients., Prog Neuropsychopharmacol Biol Psychiatry

CLOZAPINE CYP2C19

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Piatkov I et al., 2017, CYP2C19*17 protects against metabolic complications of clozapine treatment., World J Biol Psychiatry

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

CLOZAPINE JUND

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kontkanen et al., 2002, Chronic antipsychotic drug treatment induces long-lasting expression of fos and jun family genes and activator protein 1 complex in the rat prefrontal cortex., Neuropsychopharmacology

CLOZAPINE GDNF

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Shao et al., 2006, Antipsychotic drugs cause glial cell line-derived neurotrophic factor secretion from C6 glioma cells., J Psychiatry Neurosci
CLOZAPINE HLA-DRB5

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Dettling M et al., 2001, Genetic determinants of clozapine-induced agranulocytosis: recent results of HLA subtyping in a non-jewish caucasian sample., Arch Gen Psychiatry

CLOZAPINE HLA-B

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Valevski A et al., 1998, HLA-B38 and clozapine-induced agranulocytosis in Israeli Jewish schizophrenic patients., Eur J Immunogenet

Saito T et al., 2016, Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population., Biol Psychiatry

Lieberman JA et al., 1990, HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia., Arch Gen Psychiatry

CLOZAPINE SRC

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Wittmann et al., 2005, Clozapine potentiation of N-methyl-D-aspartate receptor currents in the nucleus accumbens: role of NR2B and protein kinase A/Src kinases., J. Pharmacol. Exp. Ther.
CLOZAPINE FKBP5

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Mitjans M et al., 2015, Hypothalamic-pituitary-adrenal system, neurotrophic factors and clozapine response: association with FKBP5 and NTRK2 genes., Pharmacogenet Genomics

CLOZAPINE CYP3A4

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Dragovic S et al., 2013, Characterization of human cytochrome P450s involved in the bioactivation of clozapine., Drug Metab Dispos

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

Chetty et al., 2007, CYP-mediated clozapine interactions: how predictable are they?, Curr. Drug Metab.

CLOZAPINE CNR1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Nurmi EL et al., 2013, Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies., Transl Psychiatry

Monteleone P et al., 2010, Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain., J Clin Psychopharmacol

Tiwari AK et al., 2010, A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in Schizophrenia., Neuropsychopharmacology

CLOZAPINE FASN

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Fernø et al., 2006, Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs., BMC Neurosci
CLOZAPINE SH2B1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Delacrétaz A et al., 2017, Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs., Gene
CLOZAPINE ITIH3

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Brandl EJ et al., 2016, The role of the ITIH3 rs2535629 variant in antipsychotic response., Schizophr Res

CLOZAPINE FAAH

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Monteleone P et al., 2010, Endocannabinoid Pro129Thr FAAH functional polymorphism but not 1359G/A CNR1 polymorphism is associated with antipsychotic-induced weight gain., J Clin Psychopharmacol

CLOZAPINE SLC6A3

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Xu M et al., 2010, Pharacogenetic effects of dopamine transporter gene polymorphisms on response to chlorpromazine and clozapine and on extrapyramidal syndrome in schizophrenia., Prog Neuropsychopharmacol Biol Psychiatry

CLOZAPINE PIK3CG

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kang et al., 2004, The effects of clozapine on the GSK-3-mediated signaling pathway., FEBS Lett.
CLOZAPINE COMT

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Bosia M et al., 2015, COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine., Pharmacogenomics
CLOZAPINE GCG

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Brandl EJ et al., 2014, Genetic variation in the GCG and in the GLP1R genes and antipsychotic-induced weight gain., Pharmacogenomics
CLOZAPINE HLA-C

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Dettling M et al., 2001, Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry., Pharmacogenetics
CLOZAPINE IL2

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Szuster-Ciesielska et al., Neuroleptics modulate cytokine and reactive oxygen species production in blood leukocytes of healthy volunteers., Arch. Immunol. Ther. Exp. (Warsz.)
CLOZAPINE KCNJ3

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kobayashi et al., 2000, Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes., Br. J. Pharmacol.
CLOZAPINE MTHFR

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kao AC et al., 2014, Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances., J Psychiatr Res
CLOZAPINE CYP2C9

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

CLOZAPINE ANKK1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Sukasem C et al., 2016, Impact of Pharmacogenetic Markers of CYP2D6 and DRD2 on Prolactin Response in Risperidone-Treated Thai Children and Adolescents With Autism Spectrum Disorders., J Clin Psychopharmacol

López-Rodríguez R et al., 2013, Pharmacodynamic genetic variants related to antipsychotic adverse reactions in healthy volunteers., Pharmacogenomics

Roke Y et al., 2013, The effect of the Taq1A variant in the dopamine D₂ receptor gene and common CYP2D6 alleles on prolactin levels in risperidone-treated boys., Pharmacogenet Genomics

CLOZAPINE LEP

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Atmaca et al., 2003, Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics., J Clin Psychiatry
CLOZAPINE GLP1R

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Brandl EJ et al., 2014, Genetic variation in the GCG and in the GLP1R genes and antipsychotic-induced weight gain., Pharmacogenomics
CLOZAPINE NTRK2

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Mitjans M et al., 2015, Hypothalamic-pituitary-adrenal system, neurotrophic factors and clozapine response: association with FKBP5 and NTRK2 genes., Pharmacogenet Genomics
CLOZAPINE EPM2A

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Porcelli S et al., 2016, PDE7B, NMBR and EPM2A Variants and Schizophrenia: A Case-Control and Pharmacogenetics Study., Neuropsychobiology

CLOZAPINE MC4R

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Zhang JP et al., 2016, Pharmacogenetic Associations of Antipsychotic Drug-Related Weight Gain: A Systematic Review and Meta-analysis., Schizophr Bull

Czerwensky F et al., 2013, MC4R rs489693: a clinical risk factor for second generation antipsychotic-related weight gain?, Int J Neuropsychopharmacol

Nurmi EL et al., 2013, Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies., Transl Psychiatry

CLOZAPINE GSTM1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

van der Weide K et al., 2017, Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population., Pharmacogenomics J
CLOZAPINE SLC6A4

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Kohlrausch FB et al., 2010, Influence of serotonin transporter gene polymorphisms on clozapine response in Brazilian schizophrenics., J Psychiatr Res
CLOZAPINE NT5E

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Lara et al., 2001, Chronic treatment with clozapine, but not haloperidol, increases striatal ecto-5'-nucleotidase activity in rats., Neuropsychobiology
CLOZAPINE HLA-DPB1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Dettling M et al., 2001, Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry., Pharmacogenetics
CLOZAPINE RABEP1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Delacrétaz A et al., 2017, Association of variants in SH2B1 and RABEP1 with worsening of low-density lipoprotein and glucose parameters in patients treated with psychotropic drugs., Gene
CLOZAPINE GSTT1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

van der Weide K et al., 2017, Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population., Pharmacogenomics J
CLOZAPINE GRIN2B

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Taylor DL et al., 2016, Genetic association analysis of N-methyl-D-aspartate receptor subunit gene GRIN2B and clinical response to clozapine., Hum Psychopharmacol
CLOZAPINE PRL

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Lieberman et al., 1994, Predictors of response to clozapine., J Clin Psychiatry
CLOZAPINE TBC1D1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Brandl EJ et al., 2013, Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain., Hum Psychopharmacol

CLOZAPINE CYP1A2

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

Jaquenoud Sirot E et al., 2009, ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine., J Clin Psychopharmacol

Palma BB et al., 2010, Functional characterization of eight human cytochrome P450 1A2 gene variants by recombinant protein expression., Pharmacogenomics J

CLOZAPINE ABCB1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

van der Weide K et al., 2017, Genetic risk factors for clozapine-induced neutropenia and agranulocytosis in a Dutch psychiatric population., Pharmacogenomics J

Lee ST et al., 2012, Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response., J Clin Psychopharmacol

Jaquenoud Sirot E et al., 2009, ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine., J Clin Psychopharmacol

CLOZAPINE HLA-DRB3

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Dettling M et al., 2001, Further evidence of human leukocyte antigen-encoded susceptibility to clozapine-induced agranulocytosis independent of ancestry., Pharmacogenetics

CLOZAPINE UGT1A1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Erickson-Ridout KK et al., 2012, Glucuronidation of the second-generation antipsychotic clozapine and its active metabolite N-desmethylclozapine. Potential importance of the UGT1A1 A(TA)₇TAA and UGT1A4 L48V polymorphisms., Pharmacogenet Genomics

CLOZAPINE C3

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Zhang C et al., 2017, Complement 3 and metabolic syndrome induced by clozapine: a cross-sectional study and retrospective cohort analysis., Pharmacogenomics J
CLOZAPINE GSTP1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Boerma JS et al., 2011, Application of CYP102A1M11H as a tool for the generation of protein adducts of reactive drug metabolites., Chem Res Toxicol
CLOZAPINE CBX1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CLOZAPINE DTNBP1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CLOZAPINE POLI

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
CLOZAPINE CYP2D6

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

DrugBank: DB00363

Version: 5.1.7

Alternate Names:

CLOZAPINE DrugBank Drug Name

5786-21-0 CAS Number

Aa-clozapine Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Categories adrenergic alpha-1 receptor antagonists

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Heiser et al., 2004, Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro., Prog. Neuropsychopharmacol. Biol. Psychiatry

Goldstein, 1999, Quetiapine fumarate (Seroquel): a new atypical antipsychotic., Drugs Today

TEND: CLOZAPINE
- Version: 01-August-2011
Alternate Names:

CLOZAPINE Primary Drug Name

Drug Info:

Year of Approval 1989

Drug Class antipsychotic agents

Publications:
TdgClinicalTrial: CLOZAPINE
- Version: January-2014
Alternate Names:

Drug Info:

Drug Indications Antipsychotic Agents

Drug Class small molecule

FDA Approval 1989

Publications:

NCI: CLOZAPINE

Version: 14-September-2017

Alternate Names:

C28936 NCI drug code

Drug Info:

Publications:

Lipska et al., 2003, Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs., Eur. J. Neurosci.

Schmitt et al., 2003, Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain., Neurosci. Lett.

Chetty et al., 2007, CYP-mediated clozapine interactions: how predictable are they?, Curr. Drug Metab.

DTC: CLOZAPINE

Version: 02-September-2020

Alternate Names:

CHEMBL42 ChEMBL Drug ID

Drug Info:

Publications:

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

Lacivita E et al., 2012, Investigations on the 1-(2-biphenyl)piperazine motif: identification of new potent and selective ligands for the serotonin(7) (5-HT(7)) receptor with agonist or antagonist action in vitro or ex vivo., J Med Chem

Tresadern G et al., 2011, Molecular properties affecting fast dissociation from the D2 receptor., Bioorg Med Chem

PharmGKB: clozapine

Version: 18-August-2020

Alternate Names:

Drug Info:

Publications:

Tiwari AK et al., 2010, Association study of polymorphisms in cholecystokinin gene and its receptors with antipsychotic induced weight gain in schizophrenia patients., Prog Neuropsychopharmacol Biol Psychiatry

Li T et al., 2002, Allelic association analysis of the dopamine D2, D3, 5-HT2A, and GABA(A)gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects., Am J Med Genet

Yamanouchi Y et al., 2003, Effect of DRD2, 5-HT2A, and COMT genes on antipsychotic response to risperidone., Pharmacogenomics J

TTD: Clozapine
- Version: 2020.06.01
Alternate Names:

D0Z1RV TTD Drug ID

Drug Info:

Publications:
GuideToPharmacology: 135650115
- Version: 29-September-2020
Alternate Names:

CLOZAPINE GuideToPharmacology Ligand Name

Drug Info:

Publications:
ChemblDrugs: chembl:CHEMBL42
- Version: ChEMBL_27
Alternate Names:

Drug Info:

Publications:
ChemblInteractions: CHEMBL42
- Version: chembl_23
Alternate Names:

Drug Info:

Publications:
FDA: Clozapine
- Version: 04-September-2020
Alternate Names:

Drug Info:

Publications:

Specific Action of the Ligand	Antagonist
Endogenous Drug?	False
Trial Name	-

Specific Action of the Ligand	Full agonist
Endogenous Drug?	False

Novel drug target	Established target
Trial Name	-
Specific Action of the Ligand	Antagonist

Specific Action of the Ligand	Inverse agonist
Endogenous Drug?	False
Direct Interaction?	True

CLOZAPINE	DrugBank Drug Name
5786-21-0	CAS Number
Aa-clozapine	Drug Brand

Drug Type	small molecule
Drug Groups	approved
Drug Categories	adrenergic alpha-1 receptor antagonists

CLOZAPINE Drug Record

CLOZAPINE chembl:CHEMBL42 Approved

Alternate Names:

Drug Info:

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False Trial Name -

Publications: Hwang R et al., 2007, Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response., J Psychopharmacol Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Interaction Types & Directionality: agonist (activating)

Interaction Info: Specific Action of the Ligand Full agonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Novel drug target Established target Trial Name - Specific Action of the Ligand Antagonist

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Endogenous Drug? False Specific Action of the Ligand Antagonist Novel drug target Established target

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False Trial Name -

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target Specific Action of the Ligand Inverse agonist

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Endogenous Drug? False Specific Action of the Ligand Inverse agonist

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Inverse agonist Endogenous Drug? False Direct Interaction? True

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Antagonist Endogenous Drug? False

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Endogenous Drug? False Specific Action of the Ligand Antagonist Trial Name -

Interaction Types & Directionality: agonist (activating) antagonist (inhibitory)

Interaction Info: Trial Name - Novel drug target Established target Specific Action of the Ligand Full agonist

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info:

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info:

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory) allosteric modulator

Interaction Info: Specific Action of the Ligand Positive Endogenous Drug? False

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info:

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: agonist (activating) antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Full agonist Endogenous Drug? False

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info:

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Inverse agonist Endogenous Drug? False

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Info:

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: agonist (activating) antagonist (inhibitory)

Interaction Info: Specific Action of the Ligand Full agonist Endogenous Drug? False

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: agonist (activating) antagonist (inhibitory)

Interaction Info: Endogenous Drug? False Specific Action of the Ligand Full agonist

Publications: Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality: other/unknown

Interaction Info:

Publications: Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Interaction Types & Directionality: antagonist (inhibitory)

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Trial Name -

Publications:

Hwang R et al., 2007, Association study of four dopamine D1 receptor gene polymorphisms and clozapine treatment response., J Psychopharmacol

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Interaction Types & Directionality:

agonist (activating)

Interaction Info:

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Novel drug target Established target

Trial Name -

Specific Action of the Ligand Antagonist

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Antagonist

Novel drug target Established target

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Trial Name -

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

Specific Action of the Ligand Inverse agonist

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Inverse agonist

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Inverse agonist

Endogenous Drug? False

Direct Interaction? True

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Antagonist

Endogenous Drug? False

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Antagonist

Trial Name -

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Trial Name -

Novel drug target Established target

Specific Action of the Ligand Full agonist

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

allosteric modulator

Interaction Info:

Specific Action of the Ligand Positive

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Types & Directionality:

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Inverse agonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Specific Action of the Ligand Full agonist

Endogenous Drug? False

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

agonist (activating)

antagonist (inhibitory)

Interaction Info:

Endogenous Drug? False

Specific Action of the Ligand Full agonist

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

other/unknown

Publications:

Chen et al., 2002, TTD: Therapeutic Target Database., Nucleic Acids Res.

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

antagonist (inhibitory)

Publications:

Nasrallah, 2008, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles., Mol. Psychiatry

Interaction Types & Directionality:

n/a

Publications:

Schmitt et al., 2003, Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain., Neurosci. Lett.

Interaction Types & Directionality:

n/a

Publications:

Tiwari AK et al., 2010, Association study of polymorphisms in cholecystokinin gene and its receptors with antipsychotic induced weight gain in schizophrenia patients., Prog Neuropsychopharmacol Biol Psychiatry

Interaction Types & Directionality:

n/a

Publications:

Piatkov I et al., 2017, CYP2C19*17 protects against metabolic complications of clozapine treatment., World J Biol Psychiatry

Sakatis MZ et al., 2012, Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds., Chem Res Toxicol

Interaction Types & Directionality:

n/a

Publications:

Kontkanen et al., 2002, Chronic antipsychotic drug treatment induces long-lasting expression of fos and jun family genes and activator protein 1 complex in the rat prefrontal cortex., Neuropsychopharmacology

Interaction Types & Directionality:

n/a

Publications:

Shao et al., 2006, Antipsychotic drugs cause glial cell line-derived neurotrophic factor secretion from C6 glioma cells., J Psychiatry Neurosci