Clozapine (T3D2764)

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

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

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

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

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

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

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

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

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

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

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

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