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Record Information
Version2.0
Creation Date2009-07-21 20:26:42 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2764
Identification
Common NameClozapine
ClassSmall Molecule
DescriptionA 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.
Compound Type
  • Amine
  • Antipsychotic Agent
  • Drug
  • GABA Antagonist
  • Metabolite
  • Organic Compound
  • Organochloride
  • Serotonin Antagonist
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Azaleptine
Cloment
Clonex
Clopin
Clopine
Clopsine
Clorazem
Clozapin
Clozapina
Clozapinum
Clozaril
FazaClo
Lanolept
Lapenax
Leponex
Lodux
Lozapin
Luften
Mezapin
Refract
Refraxol
Sensipin
Sequax
Sizopin
Sizopril
Syclop
Syzopin
Tanyl
Uspen
VERSACLOZ
Zapen
Zapenia
Zapine
Ziproc
Zopin
Chemical FormulaC18H19ClN4
Average Molecular Mass326.823 g/mol
Monoisotopic Mass326.130 g/mol
CAS Registry Number5786-21-0
IUPAC Name6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,9,11,13-heptaene
Traditional Nameclozapine
SMILESCN1CCN(CC1)C1=NC2=C(NC3=CC=CC=C13)C=CC(Cl)=C2
InChI IdentifierInChI=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
InChI KeyInChIKey=QZUDBNBUXVUHMW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzodiazepines. Dibenzodiazepines are compounds containing a dibenzodiazepine moiety, which consists of two benzene connected by diazepine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub ClassDibenzodiazepines
Direct ParentDibenzodiazepines
Alternative Parents
Substituents
  • Dibenzodiazepine
  • 1,4-benzodiazepine
  • N-methylpiperazine
  • N-alkylpiperazine
  • Aryl chloride
  • Aryl halide
  • 1,4-diazinane
  • Imidolactam
  • Piperazine
  • Benzenoid
  • Tertiary amine
  • Tertiary aliphatic amine
  • Amidine
  • Secondary amine
  • Organic 1,3-dipolar compound
  • Azacycle
  • Carboxylic acid amidine
  • Propargyl-type 1,3-dipolar organic compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point183-184°C
Boiling PointNot Available
Solubility11.8 mg/L
LogP3.23
Predicted Properties
PropertyValueSource
Water Solubility0.19 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 Area30.87 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity97.36 m³·mol⁻¹ChemAxon
Polarizability35.77 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-06r5-9064000000-0f31b1de88be42ac8381JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00b9-0298000000-50d2ee0b52827fd1aee3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00di-2690000000-daaa74a4f85f5e8b5926JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0090000000-bc2ca4d5a76a5facf897JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0009000000-986bc19f7e7e8602d005JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00b9-0049000000-d6315d4aeb74c251e939JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0090000000-27fd28450826291cc8c6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0290000000-474b25ea27690471db0fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-0970000000-a58015260aaddb4245bdJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-0930000000-3ccfd048a34fdb4f594fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0009000000-7df53c42e3b1618bfdecJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-004i-0049000000-7522cc8ebf988effc792JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0090000000-bd138be4ae488c201ed3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0190000000-68c8b78f304c38b7b7b5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-0980000000-a9dd724f32c02059c510JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-0930000000-61c0f65f163824ddd594JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0090000000-da747a0572aa2c21683fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-002f-0930000000-614883dbe075268cf23aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00b9-0298000000-50d2ee0b52827fd1aee3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-2690000000-daaa74a4f85f5e8b5926JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0009000000-b771968b218f574a2031JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1049000000-24dab1e16fa5778e3f05JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-2190000000-6b669cd26b101d106f1cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0009000000-178d40f752b4d092a8a6JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0029000000-5b7197f427b8cfdcdac2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-4290000000-33f870d86d2adcc8f049JSpectraViewer
Toxicity Profile
Route of ExposureOral; rapid and almost complete.
Mechanism of ToxicityThe mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) receptor antagonism. Atypical antipsychotic drugs such as clozapine have been proposed to block the 5HT2 and D2 receptors at therapeutic doses as evidenced by blockage in accelerating levels of growth hormone and cortisol secretion. The antipsychotic activity of clozapine is assumed to be the cause of D2 blockade while interacting with other receptors as well. With regards to mode of action in blocking dopaminergic receptors, clozapine exhibits higher affinity for D4 compared to the D2 receptor subtype. In addition, D1 antagonistic activity of clozapine enhances dopaminergic activity by increased extracellular brain dopamine concentrations specifically in the prefrontal cortex which is believed to explain its efficacy against negative symptoms generally observed in schizophrenia when using other drugs. Interestingly, clozapine has not been able to block arousal behavior which is the case when using other dopamine agonists after prolonged treatment. Interaction of clozapine with the immune system has also been found important when using this drug. Neutrophil apoptosis otherwise known as agranulocytosis was detected after administration of clopazine alone and bioactived clozapine to nitrenium ion at supratherapeutic and therapeutic levels, respectively. At supratherapeutic concentrations, clozapine can be toxic due to the drug itself or its stable metabolite products. At therapeutic levels however, the chemically reactive nitrenium ion is believed to bound to cellular protein, deplete intracellular GSH, and lead to final polymorphonuclear (PMN) and mononuclear leukocyte cytotoxicity in vitro. Agranulocytosis induced by bioactived clozapine can be inhibited by using antioxidants and genistein. PMN apoptosis is believed to be achieved by decelerating the life span of circulating cells after clozapine administration. Clozapine has also shown to interact with GABA receptors. Clozapine is able to induce release of glutamate and D-serine and decrease expression of glutamate transporters in astrocytic cell cultures with no neurons.
MetabolismHepatic Route of Elimination: Approximately 50% of the administered dose is excreted in the urine and 30% in the feces. Half Life: 8 hours (range 4-12 hours)
Toxicity ValuesNot Available
Lethal DoseFatal overdoses have been reported with clozapine, generally at doses above 2500 mg. There have also been reports of patients recovering from overdoses well in excess of 4 g. (13)
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use in patients with treatment-resistant schizophrenia.
Minimum Risk LevelNot Available
Health EffectsClozapine may cause side effects; most are minor, although some are serious and potentially fatal. Common side effects include extreme constipation, bed-wetting, night-time drooling, muscle stiffness, sedation, tremors, orthostatic hypotension, hyperglycemia, and weight gain. The risk of developing extrapyramidal symptoms such as tardive dyskinesia is below that of typical antipsychotics; this may be due to clozapine's anticholinergic effects. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to clozapine. Clozapine also carries five black box warnings, including warnings for agranulocytosis, CNS depression, leukopenia, neutropenia, seizure disorder, bone marrow suppression, dementia, hypotension, myocarditis, orthostatic hypotension (with or without syncope) and seizures. Lowering of the seizure threshold may be dose related and slow initial titration of dose may decrease the risk for precipitating seizures. Slow titration of dosing may also decrease the risk for orthostatic hypotension and other adverse cardiovascular side effects. Many male patients have experienced cessation of ejaculation during orgasm as a side effect of clozapine, though this is not documented in official drug guides. (Wikipedia)
SymptomsNot Available
TreatmentEstablish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. (13)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00363
HMDB IDHMDB14507
PubChem Compound ID2818
ChEMBL IDCHEMBL42
ChemSpider ID2716
KEGG IDC06924
UniProt IDNot Available
OMIM ID
ChEBI ID3766
BioCyc IDNot Available
CTD IDNot Available
Stitch IDClozapine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkClozapine
References
Synthesis Reference

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

MSDST3D2764.pdf
General References
  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. [8515788 ]
  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. [12630982 ]
  3. Naheed M, Green B: Focus on clozapine. Curr Med Res Opin. 2001;17(3):223-9. [11900316 ]
  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. [10074876 ]
  5. Baldessarini RJ, Frankenburg FR, Clozapine – A novel antipsychotic agent, The new England journal of medicine, 1991;324(11):746-54. [1671793 ]
  6. Brunello N, Masotto C, Steardo L, Markstein R, Racagni G, New insights into the biology of schizophrenia through the mechanism of action of clozapine, Neuropsychopharmacology, 1995;13(3):177–213. [8602893 ]
  7. Meltzer, H. Y., Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia, Psychopharmacology, 1989;99:S18-S27. [2682729 ]
  8. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [11873706 ]
  9. Tanahashi S, Yamamura S, Nakagawa M, Motomura E, Okada M, Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes, Br J Pharmacol, 2012;165(5):1543-55. [21880034 ]
  10. Williams DP, Pirmohamed M, Naisbitt DJ, Uetrecht JP, Park BK, Induction of Metabolism-Dependent and –Independent Neutrophil Apoptosis by Clozapine, Molecular Pharmacology, 2000;58:207–216. [10860943 ]
  11. Wu Y, Blichowski M, Daskalakis ZJ, Wu Z, Liu CC, Cortez MA, Snead OC 3rd, Evidence that clozapine directly interacts on the GABAb receptor, Neuroreport, 2011;22(13):637-641. [21753741 ]
  12. Drugs.com [Link]
  13. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.113 uMNot AvailableBindingDB 50001884
IC500.138 uMNot AvailableBindingDB 50001884
IC500.20417 uMNot AvailableBindingDB 50001884
IC500.206 uMNot AvailableBindingDB 50001884
IC500.23 uMNot AvailableBindingDB 50001884
IC500.26 uMNot AvailableBindingDB 50001884
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [14575800 ]
  3. 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. [12769622 ]
  4. 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. [15286066 ]
  5. 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. [15781964 ]
  6. 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. [16040180 ]
  7. Zhang X, Hodgetts K, Rachwal S, Zhao H, Wasley JW, Craven K, Brodbeck R, Kieltyka A, Hoffman D, Bacolod MD, Girard B, Tran J, Thurkauf A: trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents. J Med Chem. 2000 Oct 19;43(21):3923-32. [11052797 ]
  8. Morphy R, Rankovic Z: Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43. [16220969 ]
  9. McRobb FM, Crosby IT, Yuriev E, Lane JR, Capuano B: Homobivalent ligands of the atypical antipsychotic clozapine: design, synthesis, and pharmacological evaluation. J Med Chem. 2012 Feb 23;55(4):1622-34. doi: 10.1021/jm201420s. Epub 2012 Feb 2. [22243698 ]
  10. Perrone R, Berardi F, Colabufo NA, Leopoldo M, Tortorella V: N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide: a potent and selective dopamine D4 ligand. J Med Chem. 1998 Nov 19;41(24):4903-9. [9822559 ]
  11. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
  12. Kapur S, McClelland RA, VanderSpek SC, Wadenberg ML, Baker G, Nobrega J, Zipursky RB, Seeman P: Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. Neuroreport. 2002 May 7;13(6):831-5. [11997696 ]
  13. Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G: Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992 Jul;49(7):538-44. [1352677 ]
General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.009 uMNot AvailableBindingDB 50001884
IC500.017 uMNot AvailableBindingDB 50001884
IC500.023 uMNot AvailableBindingDB 50001884
IC500.052 uMNot AvailableBindingDB 50001884
IC500.058 uMNot AvailableBindingDB 50001884
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [16223700 ]
  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. [15992586 ]
  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. [15886414 ]
  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. [13129658 ]
  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. [12763097 ]
  7. Morphy R, Rankovic Z: Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43. [16220969 ]
  8. Zhang X, Hodgetts K, Rachwal S, Zhao H, Wasley JW, Craven K, Brodbeck R, Kieltyka A, Hoffman D, Bacolod MD, Girard B, Tran J, Thurkauf A: trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents. J Med Chem. 2000 Oct 19;43(21):3923-32. [11052797 ]
  9. Perrone R, Berardi F, Colabufo NA, Leopoldo M, Tortorella V: N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide: a potent and selective dopamine D4 ligand. J Med Chem. 1998 Nov 19;41(24):4903-9. [9822559 ]
  10. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
  11. Hrib NJ, Jurcak JG, Bregna DE, Burgher KL, Hartman HB, Kafka S, Kerman LL, Kongsamut S, Roehr JE, Szewczak MR, Woods-Kettelberger AT, Corbett R: Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate. J Med Chem. 1996 Sep 27;39(20):4044-57. [8831770 ]
  12. Kapur S, McClelland RA, VanderSpek SC, Wadenberg ML, Baker G, Nobrega J, Zipursky RB, Seeman P: Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. Neuroreport. 2002 May 7;13(6):831-5. [11997696 ]
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.012 uMNot AvailableBindingDB 50001884
References
  1. 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. [14530903 ]
  2. Goldstein JM: Quetiapine fumarate (Seroquel): a new atypical antipsychotic. Drugs Today (Barc). 1999 Mar;35(3):193-210. [12973385 ]
  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. [14687870 ]
  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. [14751426 ]
  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. [15037867 ]
  6. Hrib NJ, Jurcak JG, Bregna DE, Burgher KL, Hartman HB, Kafka S, Kerman LL, Kongsamut S, Roehr JE, Szewczak MR, Woods-Kettelberger AT, Corbett R: Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate. J Med Chem. 1996 Sep 27;39(20):4044-57. [8831770 ]
  7. Kapur S, McClelland RA, VanderSpek SC, Wadenberg ML, Baker G, Nobrega J, Zipursky RB, Seeman P: Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. Neuroreport. 2002 May 7;13(6):831-5. [11997696 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.15 uMNot AvailableBindingDB 50001884
References
  1. Newman-Tancredi A, Rivet JM, Cussac D, Touzard M, Chaput C, Marini L, Millan MJ: Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):188-99. Epub 2003 Aug 16. [12923612 ]
  2. 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. [12564641 ]
  3. 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. [12589516 ]
  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(1A), 5-HT(2) and 5-HT(4) receptors in rat frontal cortex. J Physiol Pharmacol. 2004 Jun;55(2):371-9. [15213359 ]
  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. [15261283 ]
  6. Taverne T, Diouf O, Depreux P, Poupaert JH, Lesieur D, Guardiola-Lemaitre B, Renard P, Rettori MC, Caignard DH, Pfeiffer B: Novel benzothiazolin-2-one and benzoxazin-3-one arylpiperazine derivatives with mixed 5HT1A/D2 affinity as potential atypical antipsychotics. J Med Chem. 1998 Jun 4;41(12):2010-8. [9622542 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.19055 uMNot AvailableBindingDB 50001884
IC500.191 uMNot AvailableBindingDB 50001884
IC500.32359 uMNot AvailableBindingDB 50001884
IC500.324 uMNot AvailableBindingDB 50001884
IC505.754 uMNot AvailableBindingDB 50001884
References
  1. Ermondi G, Visentin S, Caron G: GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers. Eur J Med Chem. 2009 May;44(5):1926-32. doi: 10.1016/j.ejmech.2008.11.009. Epub 2008 Nov 28. [19110341 ]
  2. Cavalli A, Poluzzi E, De Ponti F, Recanatini M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J Med Chem. 2002 Aug 29;45(18):3844-53. [12190308 ]
  3. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
  4. Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
  5. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
  6. Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.01 uMNot AvailableBindingDB 50001884
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. [15917433 ]
  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. [16182256 ]
  3. Taverne T, Diouf O, Depreux P, Poupaert JH, Lesieur D, Guardiola-Lemaitre B, Renard P, Rettori MC, Caignard DH, Pfeiffer B: Novel benzothiazolin-2-one and benzoxazin-3-one arylpiperazine derivatives with mixed 5HT1A/D2 affinity as potential atypical antipsychotics. J Med Chem. 1998 Jun 4;41(12):2010-8. [9622542 ]
  4. Theisen FM, Haberhausen M, Firnges MA, Gregory P, Reinders JH, Remschmidt H, Hebebrand J, Antel J: No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. Epub 2006 Sep 19. [16983399 ]
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.0031 uMNot AvailableBindingDB 50001884
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [17382376 ]
  3. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  4. Theisen FM, Haberhausen M, Firnges MA, Gregory P, Reinders JH, Remschmidt H, Hebebrand J, Antel J: No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. Epub 2006 Sep 19. [16983399 ]
General Function:
Histamine receptor activity
Specific Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
Gene Name:
HRH4
Uniprot ID:
Q9H3N8
Molecular Weight:
44495.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.0119 uMNot AvailableBindingDB 50001884
Dissociation0.0145 uMNot AvailableBindingDB 50001884
Dissociation0.0209 uMNot AvailableBindingDB 50001884
Dissociation0.0702 uMNot AvailableBindingDB 50001884
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [17346280 ]
  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. [16854056 ]
  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. [16860312 ]
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Kapur S, McClelland RA, VanderSpek SC, Wadenberg ML, Baker G, Nobrega J, Zipursky RB, Seeman P: Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. Neuroreport. 2002 May 7;13(6):831-5. [11997696 ]
  3. Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G: Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry. 1992 Jul;49(7):538-44. [1352677 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.0094 uMNot AvailableBindingDB 50001884
References
  1. Liao Y, DeBoer P, Meier E, Wikstrom H: Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic. J Med Chem. 1997 Dec 5;40(25):4146-53. [9406603 ]
  2. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
  3. Kapur S, McClelland RA, VanderSpek SC, Wadenberg ML, Baker G, Nobrega J, Zipursky RB, Seeman P: Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. Neuroreport. 2002 May 7;13(6):831-5. [11997696 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular Weight:
43567.535 Da
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. [17848919 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
Gene Name:
HTR1D
Uniprot ID:
P28221
Molecular Weight:
41906.38 Da
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. [17848919 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:
HTR1E
Uniprot ID:
P28566
Molecular Weight:
41681.57 Da
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. [17848919 ]
General Function:
Voltage-gated potassium channel activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
Gene Name:
HTR3A
Uniprot ID:
P46098
Molecular Weight:
55279.835 Da
References
  1. Rammes G, Hosp C, Eisensamer B, Tanasic S, Nothdurfter C, Zieglgansberger W, Rupprecht R: Identification of a domain which affects kinetics and antagonistic potency of clozapine at 5-HT3 receptors. PLoS One. 2009 Aug 21;4(8):e6715. doi: 10.1371/journal.pone.0006715. [19696922 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
References
  1. Theisen FM, Haberhausen M, Firnges MA, Gregory P, Reinders JH, Remschmidt H, Hebebrand J, Antel J: No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. Epub 2006 Sep 19. [16983399 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
Molecular Weight:
53554.43 Da
References
  1. Crider JY, Williams GW, Drace CD, Katoli P, Senchyna M, Sharif NA: Pharmacological characterization of a serotonin receptor (5-HT7) stimulating cAMP production in human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2003 Nov;44(11):4837-44. [14578406 ]
General Function:
G-protein coupled adenosine receptor activity
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name:
ADORA3
Uniprot ID:
P0DMS8
Molecular Weight:
36184.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.156 uMNot AvailableBindingDB 50001884
References
  1. Minetti P, Tinti MO, Carminati P, Castorina M, Di Cesare MA, Di Serio S, Gallo G, Ghirardi O, Giorgi F, Giorgi L, Piersanti G, Bartoccini F, Tarzia G: 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization. J Med Chem. 2005 Nov 3;48(22):6887-96. [16250647 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
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. [17848919 ]
General Function:
Epinephrine binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
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. [17848919 ]
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
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. [17848919 ]
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name:
DRD3
Uniprot ID:
P35462
Molecular Weight:
44224.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.45 uMNot AvailableBindingDB 50001884
References
  1. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
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. [17848919 ]
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
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. [17848919 ]
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
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. [17848919 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60073.205 Da
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. [17848919 ]
General Function:
Clathrin light chain binding
Specific Function:
Interacts with clathrin light chain A and stimulates clathrin self-assembly and clathrin-mediated endocytosis.
Gene Name:
CALY
Uniprot ID:
Q9NYX4
Molecular Weight:
23433.49 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD5
Uniprot ID:
P21918
Molecular Weight:
52950.5 Da