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Identification
NameClozapine
Accession NumberDB00363  (APRD00470)
Typesmall molecule
Groupsapproved
Description

A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
ClozapinGermanPh. Eur. 7
ClozapineNot AvailableDCF, USAN, BAN
ClozapinumLatinPh. Eur. 7
SaltsNot Available
Brand names
NameCompany
AzaleptineArpimed
ChlorpromazinePfoshen
ClomentPharmaplan
ClonexAdeka
ClopinEast West
ClopineDouglas
ClopsinePsicofarma
ClorazemRemedica
ClozapineRemedica
ClozarilNovartis
FazaCloJazz Pharmaceuticals
LanoleptLannacher
LapenaxNovartis
LeponexNovartis
LoduxRider
LozapinTorrent
LuftenPharos
MezapinPanbiotic
RefractCrescent
RefraxolAC Farma
SensipinBeximco
SequaxIvax
SizopinSun
SizoprilMeprofarm
SyclopBrown & Burk Phils
SyzopinPsyco Remedies
TanylNovamed
UspenYu Sheng
ZapenPsipharma
ZapeniaIncepta
ZapineTaiwan Biotech
ZiprocTorrent
ZopinPsychotropics India
Brand mixturesNot Available
Categories
CAS number5786-21-0
WeightAverage: 326.823
Monoisotopic: 326.129824335
Chemical FormulaC18H19ClN4
InChI KeyInChIKey=QZUDBNBUXVUHMW-UHFFFAOYSA-N
InChI
InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3
IUPAC Name
6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaene
SMILES
CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzodiazepines
SubclassDibenzodiazepines
Direct parentDibenzodiazepines
Alternative parentsChlorobenzenes; Aryl Chlorides; Diazinanes; Piperazines; Tertiary Amines; Polyamines; Carboxamidines; Secondary Amines; Organochlorides
Substituentschlorobenzene; aryl halide; aryl chloride; 1,4-diazinane; benzene; piperazine; tertiary amine; amidine; polyamine; carboxylic acid amidine; secondary amine; organohalogen; organochloride; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzodiazepines. These are compounds containing a dibenzodiazepine moiety, which consists of two benzene connected by a diazepine ring.
Pharmacology
IndicationFor use in patients with treatment-resistant schizophrenia.
PharmacodynamicsClozapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Clozapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Clozapine acts as an antagonist at other receptors, but with lower potency. Antagonism at receptors other than dopamine and 5HT2 with similar receptor affinities may explain some of the other therapeutic and side effects of Clozapine. Clozapine's antagonism of muscarinic M1-5 receptors may explain its anticholinergic effects. Clozapine's antagonism of histamine H1 receptors may explain the somnolence observed with this drug. Clozapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
Mechanism of actionClozapine's antipsychotic action is likely mediated through a combination of antogistic effects at D2 receptors in the mesolimbic pathway and 5-HT2A receptors in the frontal cortex. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms.
AbsorptionRapid and almost complete
Volume of distributionNot Available
Protein binding97% (bound to serum proteins)
Metabolism

Hepatic

SubstrateEnzymesProduct
Clozapine
NorclozapineDetails
Clozapine
Clozapine N-oxideDetails
Clozapine
Clozapine glucuronideDetails
Route of eliminationApproximately 50% of the administered dose is excreted in the urine and 30% in the feces.
Half life8 hours (range 4-12 hours)
ClearanceNot Available
ToxicityClozapine carries a black-box warning for agranulocytosis.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
Gene symbol: GNB3
UniProt: P16520
rs5443 Not AvailableTT alleleSchizophrenia patients taking this drug more more weight than patients with at least one rs5443(c) allele16141801
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9904
Blood Brain Barrier + 0.9614
Caco-2 permeable + 0.6151
P-glycoprotein substrate Substrate 0.8684
P-glycoprotein inhibitor I Inhibitor 0.6791
P-glycoprotein inhibitor II Inhibitor 0.7407
Renal organic cation transporter Inhibitor 0.8049
CYP450 2C9 substrate Non-substrate 0.7509
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.6088
CYP450 1A2 substrate Inhibitor 0.5722
CYP450 2C9 substrate Non-inhibitor 0.9432
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9137
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.571
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9106
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 3.0838 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8189
hERG inhibition (predictor II) Inhibitor 0.7164
Pharmacoeconomics
Manufacturers
  • Azur pharma international iii ltd
  • Caraco pharmaceutical laboratories ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Par pharmaceutical
  • Sandoz inc
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Fazaclo 100 mg odt6.55USDtablet
Clozapine 200 mg tablet6.32USDtablet
Clozaril 100 mg tablet5.84USDtablet
Clozapine 100 mg tablet3.33USDtablet
Apo-Clozapine 100 mg Tablet2.77USDtablet
Gen-Clozapine 100 mg Tablet2.77USDtablet
Fazaclo 25 mg odt2.4USDtablet
Fazaclo 25 mg tablet2.19USDtablet
Clozaril 25 mg tablet1.96USDtablet
Fazaclo 12.5 mg odt1.79USDtablet
Clozapine 50 mg tablet1.65USDtablet
Clozapine 25 mg tablet1.28USDtablet
Apo-Clozapine 25 mg Tablet0.69USDtablet
Gen-Clozapine 25 mg Tablet0.69USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States60249811998-04-092018-04-09
United States51788781993-01-122010-01-12
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point183-184 °CPhysProp
water solubility11.8 mg/LNot Available
logP3.23HANSCH,C ET AL. (1995)
pKa7.5EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
water solubility1.86e-01 g/lALOGPS
logP3.67ALOGPS
logP3.4ChemAxon
logS-3.2ALOGPS
pKa (strongest acidic)15.9ChemAxon
pKa (strongest basic)7.35ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area30.87ChemAxon
rotatable bond count0ChemAxon
refractivity97.36ChemAxon
polarizability35.77ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Schmutz, J. and Hunziker, F.; US. Patent 3,539,573; November 10, 1970 .

US3539573
General Reference
  1. Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA: Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993 Jul 15;329(3):162-7. Pubmed
  2. Vaddadi KS, Soosai E, Vaddadi G: Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol. 2003 Mar;55(3):307-9. Pubmed
  3. Naheed M, Green B: Focus on clozapine. Curr Med Res Opin. 2001;17(3):223-9. Pubmed
  4. Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW: Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999 Jan;60(1):36-40. Pubmed
External Links
ResourceLink
KEGG DrugD00283
KEGG CompoundC06924
PubChem Compound2818
PubChem Substance46506474
ChemSpider2716
BindingDB22869
ChEBI3766
ChEMBLCHEMBL42
Therapeutic Targets DatabaseDAP000029
PharmGKBPA449061
IUPHAR38
Guide to Pharmacology38
Drug Product Database2240669
RxListhttp://www.rxlist.com/cgi/generic3/clozapine.htm
Drugs.comhttp://www.drugs.com/clozapine.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/clo1089.shtml
WikipediaClozapine
ATC CodesN05AH02
AHFS Codes
  • 28:16.08.04
PDB EntriesNot Available
FDA labelshow(89.8 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ado-trastuzumab emtansineAvoid combination due to the increased potential for agranulocytosis.
AlprazolamIncreased risk of toxicity
BromazepamBromazepam may increase the adverse effects of clozapine. Consider alternate therapy or a reduction in the bromazepam dose. Monitor for respiratory depression and hypotension if concomitant therapy is initiated.
CaffeineCaffeine increases the effect and toxicity of clozapine
CarbamazepineCarbamazepine may decrease the serum concentration of clozapine by increasing its metabolism. Concomitant therapy should also be avoided due to increased risk of bone marrow suppression. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if carbamazepine is initiated, discontinued or dose changed.
ChlordiazepoxideIncreased risk of toxicity
CimetidineCimetidine may increase the serum concentratin of clozapine. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of clozapine if cimetidine is initiated, discontinued or dose changed.
CinolazepamIncreased risk of toxicity
CiprofloxacinCiprofloxacin may increase clozapine serum levels
CitalopramThe antidepressant increases the effect of clozapine
ClobazamIncreased risk of toxicity
ClonazepamIncreased risk of toxicity
ClorazepateIncreased risk of toxicity
DiazepamIncreased risk of toxicity
DihydrocodeineCNS depressants may enhance the adverse effects and toxicity of other CNS depressants. It is recommended to monitor therapy.
DonepezilPossible antagonism of action
ErythromycinErythromycin increases the effect of clozapine
EstazolamIncreased risk of toxicity
EthotoinHydantoin decreases the effect of clozapine
FlunitrazepamIncreased risk of toxicity
FluoxetineThe antidepressant increases the effect of clozapine
FlurazepamIncreased risk of toxicity
FluvoxamineThe antidepressant increases the effect of clozapine
FosphenytoinHydantoin decreases the effect of clozapine
GalantaminePossible antagonism of action
HalazepamIncreased risk of toxicity
HaloperidolClozapine, a moderate CYP2D6 inhibitor, may increase the serum concentration of haloperidol by decreasing its metabolism. Additive CNS despresant and anticholinergic effects may also occur. Monitor for changes in the therapeutic and adverse effects of haloperidol if clozapine is initiated, discontinued or dose changed. Also monitor for increased CNS depressant and anticholinergic effects during concomitant therapy.
JosamycinErythromycin increases the effect of clozapine
KetazolamIncreased risk of toxicity
LamotrigineLamotrigine increases the effect and toxicity of clozapine
LorazepamIncreased risk of toxicity
MephenytoinHydantoin decreases the effect of clozapine
MidazolamIncreased risk of toxicity
ModafinilModafinil increases the effect and toxicity of clozapine
NitrazepamIncreased risk of toxicity
NorfloxacinCiprofloxacin may increase clozapine serum levels
OxazepamIncreased risk of toxicity
PaclitaxelAvoid combination due to the potential enhancement of agranulocytosis by clozapine.
PhenytoinPhenytoin may decrease the effect of clozapine.
PrazepamIncreased risk of toxicity
QuazepamIncreased risk of toxicity
RifabutinRifabutin decreases the effect of clozapine
RifampicinRifampin decreases the effect of clozapine
RitonavirRitonavir increases the effect and toxicity of clozapine
RivastigminePossible antagonism of action
SertralineThe antidepressant increases the effect of clozapine
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Clozapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
TamoxifenClozapine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
TamsulosinClozapine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clozapine is initiated, discontinued, or dose changed.
TemazepamThe benzodiazepine, Temazepam, may increase the adverse effects of Clozapine. Monitor for respiratory depression and hypotension if concomitant therapy is initiated.
TetrabenazineMay cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
ThiabendazoleThe strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clozapine by decreasing Clozapine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clozapine if Thiabendazole is initiated, discontinued or dose changed.
TofacitinibAvoid combination due to the increased risk of clozapine induced agranulocytosis.
TramadolClozapine may decrease the effect of Tramadol by decreasing active metabolite production.
TriazolamIncreased risk of toxicity
TrimethobenzamideTrimethobenzamide and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineTriprolidine and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Clozapine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
VilazodoneSelective Serotonin Reuptake Inhibitors may decrease the metabolism of clozapine. If concurrent use of these agents is employed, monitor for increased toxic effects of clozapine if a selective serotonin reuptake inhibitor (SSRI) is initiated/dose increased, or decreased effects if a SSRI is discontinued/dose decreased.
Food Interactions
  • Avoid alcohol.
  • Limit caffeine intake (may reduce clozapine matabolism).
  • Take without regard to meals.

1. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. Green AI, Salomon MS, Brenner MJ, Rawlins K: Treatment of schizophrenia and comorbid substance use disorder. Curr Drug Targets CNS Neurol Disord. 2002 Apr;1(2):129-39. Pubmed
  2. Weizman T, Pick CG, Backer MM, Rigai T, Bloch M, Schreiber S: The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms. Eur J Pharmacol. 2003 Oct 8;478(2-3):155-9. Pubmed
  3. Young RM, Lawford BR, Barnes M, Burton SC, Ritchie T, Ward WK, Noble EP: Prolactin levels in antipsychotic treatment of patients with schizophrenia carrying the DRD2*A1 allele. Br J Psychiatry. 2004 Aug;185:147-51. Pubmed
  4. Stonehouse AH, Jones FS: Bromocriptine and clozapine regulate dopamine 2 receptor gene expression in the mouse striatum. J Mol Neurosci. 2005;25(1):29-36. Pubmed
  5. Takano A, Suhara T, Kusumi I, Takahashi Y, Asai Y, Yasuno F, Ichimiya T, Inoue M, Sudo Y, Koyama T: Time course of dopamine D2 receptor occupancy by clozapine with medium and high plasma concentrations. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jan;30(1):75-81. Epub 2005 Jul 22. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Goldstein JM: Quetiapine fumarate (Seroquel): a new atypical antipsychotic. Drugs Today (Barc). 1999 Mar;35(3):193-210. Pubmed
  2. McDonald LM, Moran PM, Vythelingum GN, Joseph MH, Stephenson JD, Gray JA: Enhancement of latent inhibition by two 5-HT2A receptor antagonists only when given at both pre-exposure and conditioning. Psychopharmacology (Berl). 2003 Sep;169(3-4):321-31. Epub 2002 Aug 9. Pubmed
  3. Broderick PA, Hope O, Okonji C, Rahni DN, Zhou Y: Clozapine and cocaine effects on dopamine and serotonin release in nucleus accumbens during psychostimulant behavior and withdrawal. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Jan;28(1):157-71. Pubmed
  4. Heiser P, Schulte E, Hausmann C, Becker R, Remschmidt H, Krieg JC, Vedder H: Effects of clozapine and its metabolites on the 5-HT2 receptor system in cortical and hippocampal cells in vitro. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar;28(2):297-302. Pubmed
  5. Reist C, Mazzanti C, Vu R, Fujimoto K, Goldman D: Inter-relationships of intermediate phenotypes for serotonin function, impulsivity, and a 5-HT2A candidate allele: His452Tyr. Mol Psychiatry. 2004 Sep;9(9):871-8. Pubmed
  6. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. Pubmed

3. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. D(3) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
D(3) dopamine receptor P35462 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

5. D(4) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
D(4) dopamine receptor P21917 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Zhao AL, Zhao JP, Zhang YH, Xue ZM, Chen JD, Chen XG: Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine. Int J Neurosci. 2005 Nov;115(11):1539-47. Pubmed
  3. Nakane M, Cowart MD, Hsieh GC, Miller L, Uchic ME, Chang R, Terranova MA, Donnelly-Roberts DL, Namovic MT, Miller TR, Wetter JM, Marsh K, Stewart AO, Brioni JD, Moreland RB: 2-[4-(3,4-Dimethylphenyl)piperazin-1-ylmethyl]-1H benzoimidazole (A-381393), a selective dopamine D4 receptor antagonist. Neuropharmacology. 2005 Jul;49(1):112-21. Epub 2005 Apr 1. Pubmed
  4. Kuballa G, Nowak P, Labus L, Bortel A, Dabrowska J, Swoboda M, Kwiecinski A, Kostrzewa RM, Brus R: Central effects of nafadotride, a dopamine D3 receptor antagonist, in rats. Comparison with haloperidol and clozapine. Pharmacol Rep. 2005 Mar-Apr;57(2):161-9. Pubmed
  5. Glatt SJ, Faraone SV, Tsuang MT: Schizophrenia is not associated with DRD4 48-base-pair-repeat length or individual alleles: results of a meta-analysis. Biol Psychiatry. 2003 Sep 15;54(6):629-35. Pubmed
  6. Patel S, Chapman KL, Marston D, Hutson PH, Ragan CI: Pharmacological and functional characterisation of dopamine D4 receptors in the rat retina. Neuropharmacology. 2003 Jun;44(8):1038-46. Pubmed

6. 5-hydroxytryptamine receptor 1A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1A P08908 Details

References:

  1. Hagino Y, Watanabe M: Effects of clozapine on the efflux of serotonin and dopamine in the rat brain: the role of 5-HT1A receptors. Can J Physiol Pharmacol. 2002 Dec;80(12):1158-66. Pubmed
  2. Chou YH, Halldin C, Farde L: Occupancy of 5-HT1A receptors by clozapine in the primate brain: a PET study. Psychopharmacology (Berl). 2003 Mar;166(3):234-40. Epub 2003 Feb 13. Pubmed
  3. Newman-Tancredi A, Rivet JM, Cussac D, Touzard M, Chaput C, Marini L, Millan MJ: Comparison of hippocampal G protein activation by 5-HT receptor agonists and the atypical antipsychotics clozapine and S16924. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):188-99. Epub 2003 Aug 16. Pubmed
  4. Zahorodna A, Bobula B, Grzegorzewska M, Tokarski K, Hess G: The influence of repeated administration of clozapine and haloperidol on the effects of the activation of 5-HT, 5-HT and 5-HT receptors in rat frontal cortex. J Physiol Pharmacol. 2004 Jun;55(2):371-9. Pubmed
  5. Tomic M, Kundakovic M, Butorovic B, Janac B, Andric D, Roglic G, Ignjatovic D, Kostic-Rajacic S: Pharmacological evaluation of selected arylpiperazines with atypical antipsychotic potential. Bioorg Med Chem Lett. 2004 Aug 16;14(16):4263-6. Pubmed

7. 5-hydroxytryptamine receptor 1B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1B P28222 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

8. 5-hydroxytryptamine receptor 1D

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1D P28221 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

9. 5-hydroxytryptamine receptor 1E

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 1E P28566 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

10. 5-hydroxytryptamine receptor 2C

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2C P28335 Details

References:

  1. Sodhi MS, Airey DC, Lambert W, Burnet PW, Harrison PJ, Sanders-Bush E: A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts. Mol Pharmacol. 2005 Sep;68(3):711-9. Epub 2005 May 25. Pubmed
  2. Navailles S, De Deurwaerdere P, Spampinato U: Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo. Biol Psychiatry. 2006 Mar 15;59(6):568-75. Epub 2005 Sep 22. Pubmed

11. 5-hydroxytryptamine receptor 3A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 3A P46098 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

12. 5-hydroxytryptamine receptor 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 6 P50406 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

13. 5-hydroxytryptamine receptor 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 7 P34969 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

14. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Roegge CS, Perraut C, Hao X, Levin ED: Histamine H1 receptor involvement in prepulse inhibition and memory function: relevance for the antipsychotic actions of clozapine. Pharmacol Biochem Behav. 2007 Apr;86(4):686-92. Epub 2007 Feb 22. Pubmed
  3. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. Pubmed

15. Histamine H4 receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Histamine H4 receptor Q9H3N8 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Sugata Y, Okano M, Fujiwara T, Matsumoto R, Hattori H, Yamamoto M, Nishibori M, Nishizaki K: Histamine H4 receptor agonists have more activities than H4 agonism in antigen-specific human T-cell responses. Immunology. 2007 Jun;121(2):266-75. Epub 2007 Mar 7. Pubmed
  3. Smits RA, Lim HD, Stegink B, Bakker RA, de Esch IJ, Leurs R: Characterization of the histamine H4 receptor binding site. Part 1. Synthesis and pharmacological evaluation of dibenzodiazepine derivatives. J Med Chem. 2006 Jul 27;49(15):4512-6. Pubmed
  4. Adachi N, Liu K, Motoki A, Nishibori M, Arai T: Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats. Eur J Pharmacol. 2006 Aug 21;544(1-3):181-7. Epub 2006 Jun 29. Pubmed

16. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

17. Alpha-1B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1B adrenergic receptor P35368 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

18. Alpha-2A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2A adrenergic receptor P08913 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

19. Alpha-2B adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2B adrenergic receptor P18089 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

20. Alpha-2C adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Alpha-2C adrenergic receptor P18825 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

21. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

22. Muscarinic acetylcholine receptor M2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

23. Muscarinic acetylcholine receptor M3

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M3 P20309 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

24. Muscarinic acetylcholine receptor M4

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M4 P08173 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

25. Muscarinic acetylcholine receptor M5

Kind: protein

Organism: Human

Pharmacological action: no

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M5 P08912 Details

References:

  1. Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. Pubmed

26. Neuron-specific vesicular protein calcyon

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
Neuron-specific vesicular protein calcyon Q9NYX4 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Brosen K: Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet. 1995;29 Suppl 1:20-5. Pubmed
  2. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  5. Fang J, Coutts RT, McKenna KF, Baker GB: Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):592-9. Pubmed
  6. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  7. Carrillo JA, Benitez J: Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet. 2000 Aug;39(2):127-53. Pubmed

2. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2A6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2A6 P11509 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Dimethylaniline monooxygenase [N-oxide-forming] 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Dimethylaniline monooxygenase [N-oxide-forming] 3 P31513 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

9. UDP-glucuronosyltransferase 1-4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-4 P22310 Details

References:

  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

10. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

11. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

12. Cytochrome P450 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Boulton DW, DeVane CL, Liston HL, Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 2002 May 31;71(2):163-9. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on April 09, 2014 12:34