Olanzapine (T3D2754)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (36)XML
Targets (36)
Record Information
Version2.0
Creation Date2009-07-21 20:26:38 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2754
Identification
Common NameOlanzapine
ClassSmall Molecule
DescriptionOlanzapine was the third atypical antipsychotic to gain approval by the Food and Drug Administration (FDA) and has become one of the most commonly used atypical antipsychotics. Olanzapine has been approved by the FDA for the treatment of schizophrenia, acute mania in bipolar disorder, agitation associated with schizophrenia and bipolar disorder, and as maintenance treatment in bipolar disorder and psychotic depression. It has also been established in treating depression off-label because of its mood-stabilizing properties and its ability to increase the efficacy of antidepressants. Olanzapine is manufactured and marketed by the pharmaceutical company Eli Lilly and Company. It is available as a pill that comes in the strengths of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg and as as Zydis orally disintegrating tablets in the strengths of 5 mg, 10 mg, 15 mg, and 20 mg. It is also available as a rapid-acting intramuscular injection for short term acute use. Olanzapine (oh-LAN-za-peen, sold as Zyprexa, Zydis, or in combination with fluoxetine, as Symbyax) was the third atypical antipsychotic to gain approval by the Food and Drug Administration (FDA) and has become one of the most commonly used atypical antipsychotics. Olanzapine has been approved by the FDA for the treatment of schizophrenia, acute mania in bipolar disorder, agitation associated with schizophrenia and bipolar disorder, and as maintenance treatment in bipolar disorder and psychotic depression.
Compound Type
  • Amine
  • Antiemetic
  • Antipsychotic Agent
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(S)-(−)-Omeprazole
(S)-Omeprazole
(−)-Omeprazole
2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
Aedon
Amulsin
Apisco
Apsico
Arkolamyl
Caprilon
CO Olanzapine
Deprex
Dominazol
Dopin
Egolanza
Elynza
Frenial
Jolyon-MD
Kozylex
Lanopin
Lanzac
Lanzapin
Lanzep
Lapenza
Lapozan
Lazapix
Olanzapin
Olanzapina
Olanzapinum
Zyprexa
Zyprexa Intramuscular
Zyprexa Zydis
Chemical FormulaC17H20N4S
Average Molecular Mass312.433 g/mol
Monoisotopic Mass312.141 g/mol
CAS Registry Number132539-06-1
IUPAC Name5-methyl-8-(4-methylpiperazin-1-yl)-4-thia-2,9-diazatricyclo[8.4.0.0³,⁷]tetradeca-1(14),3(7),5,8,10,12-hexaene
Traditional Namezyprexa
SMILESCN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2
InChI IdentifierInChI=1S/C17H20N4S/c1-12-11-13-16(21-9-7-20(2)8-10-21)18-14-5-3-4-6-15(14)19-17(13)22-12/h3-6,11,19H,7-10H2,1-2H3
InChI KeyInChIKey=KVWDHTXUZHCGIO-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub ClassNot Available
Direct ParentBenzodiazepines
Alternative Parents
Substituents
  • Benzodiazepine
  • Thieno-para-diazepine
  • 2,3,5-trisubstituted thiophene
  • Para-diazepine
  • N-methylpiperazine
  • N-alkylpiperazine
  • N-arylated-2-aminothiophene
  • 1,4-diazinane
  • Piperazine
  • 2-aminothiophene
  • Benzenoid
  • Imidolactam
  • Heteroaromatic compound
  • Thiophene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Secondary amine
  • Amidine
  • Carboxylic acid amidine
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point195°C
Boiling PointNot Available
SolubilityNot Available
LogP2
Predicted Properties
PropertyValueSource
Water Solubility0.094 g/LALOGPS
logP3.61ALOGPS
logP3.39ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)14.17ChemAxon
pKa (Strongest Basic)7.24ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area30.87 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity93.87 m³·mol⁻¹ChemAxon
Polarizability35.37 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0btd-8090000000-3a1771a0db51f3e9472b2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03dj-0940000000-1103f40c5bb833e129032017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03dj-0940000000-37cb2e8fb99c38b097b82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-2790000000-bdc5a34b08715b752eef2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0009000000-256a6e976b00468fe8392017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0049000000-83ee647255e8d18f2b5c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0090000000-81810b42dccae4ee9ab62017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0bt9-0490000000-8994262c6a309d6637132017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-01ot-0950000000-ceb0ca01cefbd1da57d72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0149000000-e74851873e2fbaa6c1822017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03dj-0940000000-1103f40c5bb833e129032017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03dj-0940000000-37cb2e8fb99c38b097b82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0149000000-338b982664cf3019be132017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-2790000000-bdc5a34b08715b752eef2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-01ot-0950000000-fe416acb0e50253f8d172021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0bt9-0490000000-a203abf5daf6a6c6e0692021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-03di-0049000000-4b7427c44443aab6c7a12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0a4i-0090000000-15b5422aefe3fc3729562021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-03di-0009000000-d71ce384c72fd5835dac2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-01ot-0950000000-7ba8fbea8f79ae64960d2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0019000000-66bcbe5560546ebe79ae2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0097000000-7386f41b1226646553902016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03k9-5980000000-82c2110f56cd7202848e2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0039000000-01aa4f818b0cb4798c0f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0300-0092000000-cee214399c7899dbbc412016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a6u-2490000000-dec2f8d13b50769ec96e2016-08-03View Spectrum
Toxicity Profile
Route of ExposureIntramuscular, Oral. Well absorbed, with approximately 40% of the dose metabolized before reaching the systemic circulation.
Mechanism of ToxicityOlanzapine's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia. Olanzapine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Olanzapine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Olanzapine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with olanzapine.
MetabolismHepatic Route of Elimination: It is eliminated extensively by first pass metabolism, with approximately 40% of the dose metabolized before reaching the systemic circulation. Following a single oral dose of 14C labeled olanzapine, 7% of the dose of olanzapine was recovered in the urine as unchanged drug, indicating that olanzapine is highly metabolized. Half Life: 21 to 54 hours
Toxicity ValuesNot Available
Lethal DoseDeath has been reported after an acute overdose of 0.45 g, but also survival after an acute overdose of 1500 g. (6)
Carcinogenicity (IARC Classification)Not listed by IARC.
Uses/SourcesFor the acute and maintenance treatment of schizophrenia and related psychotic disorders, as well as acute treatment of manic or mixed episodes of bipolar 1 disorder. Intramuscular olanzapine is indicated for the rapid control of agitated patients.
Minimum Risk LevelNot Available
Health EffectsThe principal side effect of olanzapine is weight gain, which may be profound in some cases and/or associated with derangement in the blood lipid and blood sugar profiles. Extrapyramidal side effects, although potentially serious, are infrequent to rare from olanzapine but may include tremors and muscle rigidity. Several patient groups are at a heightened risk of side effects from olanzapine and antipsychotics in general. Olanzapine may produce non-trivial hyperglycemia in patients with diabetes mellitus. Likewise, the elderly are at a greater risk of falls and accidental injury. Young males appear to be at heightened risk of dystonic reactions, although these are relatively rare with olanzapine. Most antipsychotics, including olanzapine, may disrupt the body's natural thermoregulatory systems, thus permitting excursions to dangerous levels when situations (exposure to heat, strenuous exercise) occur. While olanzapine is used therapeutically to treat serious mental illness, occasionally it can have the opposite effect and provoke serious paradoxical reactions in a small subgroup of people, with the drug causing unusual changes in personality, thoughts or behavior; hallucinations and suicidal ideation have also been linked to olanzapine use. The U.S. Food and Drug Administration requires all atypical antipsychotics to include a warning about the risk of developing hyperglycemia and diabetes, both of which are factors in the metabolic syndrome. These effects may be related to the drugs' ability to induce weight gain, although there are some reports of metabolic changes in the absence of weight gain. Olanzapine has demonstrated carcinogenic effects in multiple studies when exposed chronically to female mice and rats, but not male mice and rats. The tumors found were in either the liver or mammary glands of the animals. Symptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Death may result from acute overdose. (Wikipedia)
SymptomsSymptoms of an overdose include tachycardia, agitation, dysarthria, decreased consciousness and coma. Death has been reported after an acute overdose of 0.45g, but also survival after an acute overdose of 1500g.
TreatmentIn case of acute overdose, establish and maintain an airway and ensure adequate ventilation, which may include intubation. Induction of emesis is not recommended as the possibility of obtundation, seizures, or dystonic reactions of the head and neck following overdose may create a risk for aspiration. Gastric lavage (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. (13)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00334
HMDB IDHMDB05012
PubChem Compound ID4585
ChEMBL IDCHEMBL715
ChemSpider ID10442212
KEGG IDC07322
UniProt IDNot Available
OMIM ID
ChEBI ID7735
BioCyc IDNot Available
CTD IDNot Available
Stitch IDOlanzapine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOlanzapine
References
Synthesis Reference

Charles Arthur Bunnell, Samuel Dean Larsen, John Richard Nichols, Susan Marie Reutzel, Gregory Alan Stephenson, “Intermediates and process for preparing olanzapine.” U.S. Patent US6020487, issued September, 1996.

MSDSLink
General References
  1. de Haan L, van Amelsvoort T, Rosien K, Linszen D: Weight loss after switching from conventional olanzapine tablets to orally disintegrating olanzapine tablets. Psychopharmacology (Berl). 2004 Sep;175(3):389-90. [15322727 ]
  2. Pollack MH, Simon NM, Zalta AK, Worthington JJ, Hoge EA, Mick E, Kinrys G, Oppenheimer J: Olanzapine augmentation of fluoxetine for refractory generalized anxiety disorder: a placebo controlled study. Biol Psychiatry. 2006 Feb 1;59(3):211-5. Epub 2005 Sep 1. [16139813 ]
  3. Sepede G, De Berardis D, Gambi F, Campanella D, La Rovere R, D'Amico M, Cicconetti A, Penna L, Peca S, Carano A, Mancini E, Salerno RM, Ferro FM: Olanzapine augmentation in treatment-resistant panic disorder: a 12-week, fixed-dose, open-label trial. J Clin Psychopharmacol. 2006 Feb;26(1):45-9. [16415705 ]
  4. Jakovljevic M, Sagud M, Mihaljevic-Peles A: Olanzapine in the treatment-resistant, combat-related PTSD--a series of case reports. Acta Psychiatr Scand. 2003 May;107(5):394-6; discussion 396. [12752037 ]
  5. McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller TJ, Woods SW, Hawkins KA, Hoffman R, Lindborg S, Tohen M, Breier A: The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design. Schizophr Res. 2003 May 1;61(1):7-18. [12648731 ]
  6. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  7. Cerdan LF, Guevara MA, Sanz A, Amezcua C, Ramos-Loyo J: Brain electrical activity changes in treatment refractory schizophrenics after olanzapine treatment. Int J Psychophysiol. 2005 Jun;56(3):237-47. [15866327 ]
  8. Horak EL, Jenkins AJ: Postmortem tissue distribution of olanzapine and citalopram in a drug intoxication. J Forensic Sci. 2005 May;50(3):679-81. [15932107 ]
  9. Yamada K, Isotani T, Irisawa S, Yoshimura M, Tajika A, Yagyu T, Saito A, Kinoshita T: EEG Global Field Power spectrum changes after a single dose of atypical antipsychotics in healthy volunteers. Brain Topogr. 2004 Summer;16(4):281-5. [15379228 ]
  10. Mortimer A, Martin S, Loo H, Peuskens J: A double-blind, randomized comparative trial of amisulpride versus olanzapine for 6 months in the treatment of schizophrenia. Int Clin Psychopharmacol. 2004 Mar;19(2):63-9. [15076013 ]
  11. Merrick TC, Felo JA, Jenkins AJ: Tissue distribution of olanzapine in a postmortem case. Am J Forensic Med Pathol. 2001 Sep;22(3):270-4. [11563738 ]
  12. Drugs.com [Link]
  13. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. 5-hydroxytryptamine receptor 2A
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
Inhibitory0.0019 uMNot AvailableBindingDB 50053711
Inhibitory0.0023 uMNot AvailableBindingDB 50053711
Inhibitory0.0033 uMNot AvailableBindingDB 50053711
Inhibitory0.004 uMNot AvailableBindingDB 50053711
IC500.007 uMNot AvailableBindingDB 50053711
IC500.009 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. [14530903 ]
  3. Moresco RM, Cavallaro R, Messa C, Bravi D, Gobbo C, Galli L, Lucignani G, Colombo C, Rizzo G, Velona I, Smeraldi E, Fazio F: Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine. J Psychopharmacol. 2004 Sep;18(3):355-65. [15358979 ]
  4. Sharpley AL, Attenburrow ME, Hafizi S, Cowen PJ: Olanzapine increases slow wave sleep and sleep continuity in SSRI-resistant depressed patients. J Clin Psychiatry. 2005 Apr;66(4):450-4. [15816787 ]
  5. Yatham LN, Goldstein JM, Vieta E, Bowden CL, Grunze H, Post RM, Suppes T, Calabrese JR: Atypical antipsychotics in bipolar depression: potential mechanisms of action. J Clin Psychiatry. 2005;66 Suppl 5:40-8. [16038601 ]
  6. Padin JF, Rodriguez MA, Dominguez E, Dopeso-Reyes IG, Buceta M, Cano E, Sotelo E, Brea J, Caruncho HJ, Isabel Cadavid M, Castro M, Isabel Loza M: Parallel regulation by olanzapine of the patterns of expression of 5-HT2A and D3 receptors in rat central nervous system and blood cells. Neuropharmacology. 2006 Sep;51(4):923-32. Epub 2006 Aug 14. [16905159 ]
  7. Gao M, Shi Z, Wang M, Zheng QH: [11C]olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand. Bioorg Med Chem Lett. 2013 Apr 1;23(7):1953-6. doi: 10.1016/j.bmcl.2013.02.045. Epub 2013 Feb 14. [23466228 ]
  8. 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 ]
  9. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  10. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
  11. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
  12. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  13. Heffernan GD, Coghlan RD, Manas ES, McDevitt RE, Li Y, Mahaney PE, Robichaud AJ, Huselton C, Alfinito P, Bray JA, Cosmi SA, Johnston GH, Kenney T, Koury E, Winneker RC, Deecher DC, Trybulski EJ: Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles. Bioorg Med Chem. 2009 Nov 15;17(22):7802-15. doi: 10.1016/j.bmc.2009.09.023. Epub 2009 Sep 18. [19836247 ]
  14. Melkersson KI, Gunes A, Dahl ML: Impact of serotonin receptor 2A gene haplotypes on C-peptide levels in clozapine- and olanzapine-treated patients. Hum Psychopharmacol. 2010 Jun-Jul;25(4):347-52. doi: 10.1002/hup.1114. [20521326 ]
Target Details
2. D(2) dopamine receptor
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
Inhibitory0.0021 uMNot AvailableBindingDB 50053711
Inhibitory0.0061 uMNot AvailableBindingDB 50053711
Inhibitory0.011 uMNot AvailableBindingDB 50053711
Inhibitory0.017 uMNot AvailableBindingDB 50053711
Inhibitory0.02 uMNot AvailableBindingDB 50053711
Inhibitory0.032 uMNot AvailableBindingDB 50053711
Inhibitory0.078 uMNot AvailableBindingDB 50053711
IC500.01 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Naiker DV, Catts SV, Catts VS, Bedi KS, Bryan-Lluka LJ: Dose determination of haloperidol, risperidone and olanzapine using an in vivo dopamine D2-receptor occupancy method in the rat. Eur J Pharmacol. 2006 Jul 1;540(1-3):87-90. Epub 2006 May 11. [16730699 ]
  3. 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 ]
  4. Jordan S, Regardie K, Johnson JL, Chen R, Kambayashi J, McQuade R, Kitagawa H, Tadori Y, Kikuchi T: In vitro functional characteristics of dopamine D2 receptor partial agonists in second and third messenger-based assays of cloned human dopamine D2Long receptor signalling. J Psychopharmacol. 2007 Aug;21(6):620-7. Epub 2006 Nov 8. [17092971 ]
  5. Thacker SK, Perna MK, Ward JJ, Schaefer TL, Williams MT, Kostrzewa RM, Brown RW: The effects of adulthood olanzapine treatment on cognitive performance and neurotrophic factor content in male and female rats neonatally treated with quinpirole. Eur J Neurosci. 2006 Oct;24(7):2075-83. [17067304 ]
  6. Lencz T, Robinson DG, Xu K, Ekholm J, Sevy S, Gunduz-Bruce H, Woerner MG, Kane JM, Goldman D, Malhotra AK: DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients. Am J Psychiatry. 2006 Mar;163(3):529-31. [16513877 ]
  7. Gao M, Shi Z, Wang M, Zheng QH: [11C]olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand. Bioorg Med Chem Lett. 2013 Apr 1;23(7):1953-6. doi: 10.1016/j.bmcl.2013.02.045. Epub 2013 Feb 14. [23466228 ]
  8. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  9. Pettersson F, Ponten H, Waters N, Waters S, Sonesson C: Synthesis and evaluation of a set of 4-phenylpiperidines and 4-phenylpiperazines as D2 receptor ligands and the discovery of the dopaminergic stabilizer 4-[3-(methylsulfonyl)phenyl]-1-propylpiperidine (huntexil, pridopidine, ACR16). J Med Chem. 2010 Mar 25;53(6):2510-20. doi: 10.1021/jm901689v. [20155917 ]
  10. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
  11. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  12. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
  13. de Haan L, Lavalaye J, Linszen D, Dingemans PM, Booij J: Subjective experience and striatal dopamine D(2) receptor occupancy in patients with schizophrenia stabilized by olanzapine or risperidone. Am J Psychiatry. 2000 Jun;157(6):1019-20. [10831489 ]
  14. Arakawa R, Okumura M, Ito H, Takano A, Takahashi H, Takano H, Maeda J, Okubo Y, Suhara T: Positron emission tomography measurement of dopamine D(2) receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. J Clin Psychiatry. 2010 Sep;71(9):1131-7. doi: 10.4088/JCP.08m04307yel. Epub 2010 Feb 23. [20361897 ]
Target Details
3. 5-hydroxytryptamine receptor 2C
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
Inhibitory0.0028 uMNot AvailableBindingDB 50053711
Inhibitory0.0071 uMNot AvailableBindingDB 50053711
Inhibitory0.01 uMNot AvailableBindingDB 50053711
Inhibitory0.011 uMNot AvailableBindingDB 50053711
Inhibitory0.014 uMNot AvailableBindingDB 50053711
IC500.071 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Wood MD, Scott C, Clarke K, Cato KJ, Patel N, Heath J, Worby A, Gordon L, Campbell L, Riley G, Davies CH, Gribble A, Jones DN: Pharmacological profile of antipsychotics at monoamine receptors: atypicality beyond 5-HT2A receptor blockade. CNS Neurol Disord Drug Targets. 2006 Aug;5(4):445-52. [16918396 ]
  3. Zhang JY, Kowal DM, Nawoschik SP, Lou Z, Dunlop J: Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms. Biochem Pharmacol. 2006 Feb 14;71(4):521-9. Epub 2005 Dec 5. [16336943 ]
  4. Overstreet DH, Knapp DJ, Breese GR: Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats. Alcohol Clin Exp Res. 2007 Sep;31(9):1473-81. Epub 2007 Jul 11. [17624999 ]
  5. 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 ]
  6. Hertel P: Comparing sertindole to other new generation antipsychotics on preferential dopamine output in limbic versus striatal projection regions: mechanism of action. Synapse. 2006 Dec 1;60(7):543-52. [16952163 ]
  7. Gao M, Shi Z, Wang M, Zheng QH: [11C]olanzapine, radiosynthesis and lipophilicity of a new potential PET 5-HT2 and D2 receptor radioligand. Bioorg Med Chem Lett. 2013 Apr 1;23(7):1953-6. doi: 10.1016/j.bmcl.2013.02.045. Epub 2013 Feb 14. [23466228 ]
  8. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  9. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
  10. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  11. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
  12. Krogsgaard-Larsen N, Jensen AA, Kehler J: Novel 7-phenylsulfanyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indoles as dual serotonin 5-HT2C and 5-HT6 receptor ligands. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5431-3. doi: 10.1016/j.bmcl.2010.07.105. Epub 2010 Aug 3. [20719507 ]
Target Details
4. Histamine H1 receptor
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
Inhibitory0.0012 uMNot AvailableBindingDB 50053711
Inhibitory0.0028 uMNot AvailableBindingDB 50053711
Inhibitory0.0035 uMNot AvailableBindingDB 50053711
Inhibitory0.0056 uMNot AvailableBindingDB 50053711
Dissociation0.000087 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Poyurovsky M, Pashinian A, Levi A, Weizman R, Weizman A: The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients. Int Clin Psychopharmacol. 2005 Mar;20(2):101-3. [15729086 ]
  3. Rasmussen K, Benvenga MJ, Bymaster FP, Calligaro DO, Cohen IR, Falcone JF, Hemrick-Luecke SK, Martin FM, Moore NA, Nisenbaum LK, Schaus JM, Sundquist SJ, Tupper DE, Wiernicki TR, Nelson DL: Preclinical pharmacology of FMPD [6-fluoro-10-[3-(2-methoxyethyl)-4-methyl-piperazin-1-yl]-2-methyl-4H-3-thia-4,9- diaza-benzo[f]azulene]: a potential novel antipsychotic with lower histamine H1 receptor affinity than olanzapine. J Pharmacol Exp Ther. 2005 Dec;315(3):1265-77. Epub 2005 Sep 1. [16141369 ]
  4. Altschuler EL, Kast RE: Using histamine (H1) antagonists, in particular atypical antipsychotics, to treat anemia of chronic disease via interleukin-6 suppression. Med Hypotheses. 2005;65(1):65-7. [15893120 ]
  5. 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 ]
  6. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
  7. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  8. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
  9. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  10. 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 ]
Target Details
5. D(3) dopamine receptor
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
Inhibitory0.039 uMNot AvailableBindingDB 50053711
Inhibitory0.043 uMNot AvailableBindingDB 50053711
Inhibitory0.045 uMNot AvailableBindingDB 50053711
Inhibitory0.049 uMNot AvailableBindingDB 50053711
Inhibitory0.054 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Campiani G, Butini S, Fattorusso C, Trotta F, Gemma S, Catalanotti B, Nacci V, Fiorini I, Cagnotto A, Mereghetti I, Mennini T, Minetti P, Di Cesare MA, Stasi MA, Di Serio S, Ghirardi O, Tinti O, Carminati P: Novel atypical antipsychotic agents: rational design, an efficient palladium-catalyzed route, and pharmacological studies. J Med Chem. 2005 Mar 24;48(6):1705-8. [15771414 ]
  3. Butini S, Gemma S, Campiani G, Franceschini S, Trotta F, Borriello M, Ceres N, Ros S, Coccone SS, Bernetti M, De Angelis M, Brindisi M, Nacci V, Fiorini I, Novellino E, Cagnotto A, Mennini T, Sandager-Nielsen K, Andreasen JT, Scheel-Kruger J, Mikkelsen JD, Fattorusso C: Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior. J Med Chem. 2009 Jan 8;52(1):151-69. doi: 10.1021/jm800689g. [19072656 ]
  4. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
  5. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  6. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  7. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
Target Details
6. D(4) dopamine receptor
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
Inhibitory0.028 uMNot AvailableBindingDB 50053711
Inhibitory0.029 uMNot AvailableBindingDB 50053711
Inhibitory0.05 uMNot AvailableBindingDB 50053711
IC500.173 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Hutchison KE, Ray L, Sandman E, Rutter MC, Peters A, Davidson D, Swift R: The effect of olanzapine on craving and alcohol consumption. Neuropsychopharmacology. 2006 Jun;31(6):1310-7. [16237394 ]
  3. 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 ]
  4. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  5. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
  6. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
Target Details
7. Potassium voltage-gated channel subfamily H member 2
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
Inhibitory36 uMNot AvailableBindingDB 50053711
IC500.181 uMNot AvailableBindingDB 50053711
IC500.18197 uMNot AvailableBindingDB 50053711
IC500.182 uMNot AvailableBindingDB 50053711
References
  1. Thai KM, Ecker GF: A binary QSAR model for classification of hERG potassium channel blockers. Bioorg Med Chem. 2008 Apr 1;16(7):4107-19. doi: 10.1016/j.bmc.2008.01.017. Epub 2008 Jan 16. [18243713 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Butini S, Gemma S, Campiani G, Franceschini S, Trotta F, Borriello M, Ceres N, Ros S, Coccone SS, Bernetti M, De Angelis M, Brindisi M, Nacci V, Fiorini I, Novellino E, Cagnotto A, Mennini T, Sandager-Nielsen K, Andreasen JT, Scheel-Kruger J, Mikkelsen JD, Fattorusso C: Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior. J Med Chem. 2009 Jan 8;52(1):151-69. doi: 10.1021/jm800689g. [19072656 ]
  6. Butini S, Campiani G, Franceschini S, Trotta F, Kumar V, Guarino E, Borrelli G, Fiorini I, Novellino E, Fattorusso C, Persico M, Orteca N, Sandager-Nielsen K, Jacobsen TA, Madsen K, Scheel-Kruger J, Gemma S: Discovery of bishomo(hetero)arylpiperazines as novel multifunctional ligands targeting dopamine D(3) and serotonin 5-HT(1A) and 5-HT(2A) receptors. J Med Chem. 2010 Jun 24;53(12):4803-7. doi: 10.1021/jm100294b. [20481570 ]
Target Details
8. Muscarinic acetylcholine receptor M1
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
Inhibitory0.0021 uMNot AvailableBindingDB 50053711
Inhibitory0.0047 uMNot AvailableBindingDB 50053711
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  4. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  5. 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 ]
Target Details
9. 5-hydroxytryptamine receptor 6
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.006 uMNot AvailableBindingDB 50053711
Inhibitory0.01 uMNot AvailableBindingDB 50053711
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 ]
  2. Krogsgaard-Larsen N, Jensen AA, Kehler J: Novel 7-phenylsulfanyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indoles as dual serotonin 5-HT2C and 5-HT6 receptor ligands. Bioorg Med Chem Lett. 2010 Sep 15;20(18):5431-3. doi: 10.1016/j.bmcl.2010.07.105. Epub 2010 Aug 3. [20719507 ]
  3. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  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 ]
Target Details
10. D(1A) dopamine receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01 uMNot AvailableBindingDB 50053711
Inhibitory0.052 uMNot AvailableBindingDB 50053711
Inhibitory0.25 uMNot AvailableBindingDB 50053711
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
  3. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  4. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
Target Details
11. 5-hydroxytryptamine receptor 1A
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
Inhibitory2.1 uMNot AvailableBindingDB 50053711
Inhibitory7.1 uMNot AvailableBindingDB 50053711
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 ]
  2. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]
  3. Rowley M, Bristow LJ, Hutson PH: Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501. [11170639 ]
Target Details
12. 5-hydroxytryptamine receptor 7
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.365 uMNot AvailableBindingDB 50053711
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 ]
  2. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
Target Details
13. Alpha-1A adrenergic receptor
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
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 ]
  2. Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO: Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. Schizophr Res. 1999 May 4;37(1):107-22. [10227113 ]
Target Details
14. Alpha-2A adrenergic receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.192 uMNot AvailableBindingDB 50053711
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 ]
  2. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
Target Details
15. Alpha-2C adrenergic receptor
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.082 uMNot AvailableBindingDB 50053711
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 ]
  2. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
16. D(1) dopamine receptor (Protein Group)
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Included Proteins:
P21728 , P21918
References
  1. Fernandez J, Alonso JM, Andres JI, Cid JM, Diaz A, Iturrino L, Gil P, Megens A, Sipido VK, Trabanco AA: Discovery of new tetracyclic tetrahydrofuran derivatives as potential broad-spectrum psychotropic agents. J Med Chem. 2005 Mar 24;48(6):1709-12. [15771415 ]
  2. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
Target Details
17. D(1B) dopamine receptor
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
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 ]
  2. Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO: Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. Schizophr Res. 1999 May 4;37(1):107-22. [10227113 ]
Target Details
18. Muscarinic acetylcholine receptor M2
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
19. Muscarinic acetylcholine receptor M3
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
20. Muscarinic acetylcholine receptor M4
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
21. Muscarinic acetylcholine receptor M5
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
22. 5-hydroxytryptamine receptor 1B
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 ]
Target Details
23. 5-hydroxytryptamine receptor 1D
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 ]
Target Details
24. 5-hydroxytryptamine receptor 1E
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 ]
Target Details
25. 5-hydroxytryptamine receptor 2B
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives 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. 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. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:
HTR2B
Uniprot ID:
P41595
Molecular Weight:
54297.41 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
Target Details
26. 5-hydroxytryptamine receptor 3A
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. 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 ]
Target Details
27. 5-hydroxytryptamine receptor 5A
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.
Gene Name:
HTR5A
Uniprot ID:
P47898
Molecular Weight:
40254.69 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
Target Details
28. Alpha-1B adrenergic receptor
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Target Details
29. Alpha-2B adrenergic receptor
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 ]
30. Beta adrenergic receptor (Protein Group)
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Included Proteins:
P08588 , P07550 , P13945
References
  1. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT: Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996 Feb;14(2):87-96. [8822531 ]
31. D(2L) dopamine receptor
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
32. D(2S) dopamine receptor
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
33. GABA-A receptor (anion channel) (Protein Group)
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Included Proteins:
P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88
References
  1. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT: Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996 Feb;14(2):87-96. [8822531 ]
Target Details
34. Histamine H2 receptor
General Function:
Histamine receptor activity
Specific Function:
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).
Gene Name:
HRH2
Uniprot ID:
P25021
Molecular Weight:
40097.65 Da
References
  1. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
Target Details
35. Histamine H4 receptor
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. Shahid M, Walker GB, Zorn SH, Wong EH: Asenapine: a novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol. 2009 Jan;23(1):65-73. doi: 10.1177/0269881107082944. Epub 2008 Feb 28. [18308814 ]
Target Details
36. Sodium-dependent serotonin transporter
General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>15 uMNot AvailableBindingDB 50053711
References
  1. Ablordeppey SY, Altundas R, Bricker B, Zhu XY, Kumar EV, Jackson T, Khan A, Roth BL: Identification of a butyrophenone analog as a potential atypical antipsychotic agent: 4-[4-(4-chlorophenyl)-1,4-diazepan-1-yl]-1-(4-fluorophenyl)butan-1-one. Bioorg Med Chem. 2008 Aug 1;16(15):7291-301. doi: 10.1016/j.bmc.2008.06.030. Epub 2008 Jun 20. [18595716 ]