Quetiapine (T3D2555)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (30)XML
Targets (30)
Record Information
Version2.0
Creation Date2009-07-05 02:44:12 UTC
Update Date2014-12-24 20:25:41 UTC
Accession NumberT3D2555
Identification
Common NameQuetiapine
ClassSmall Molecule
DescriptionThe most common side effect is sedation, and is prescribed specifically for this effect in patients with sleep disorders. Seroquel will put the patient into a drowsy state, and will help the patient fall asleep. It is one of the most sedating of all anti psychotic drugs, rivaling even the most sedating older antipsychotics. Many prescriptions call for the entire dose to be taken before bedtime because of its sedative effects. Although quetiapine is approved by the FDA for the treatment of schizophrenia and bipolar disorder, it is frequently prescribed for off-label purposes including insomnia or the treatment of anxiety disorders. Due to its sedative side effects, reports of quetiapine abuse (sometimes by insufflating crushed tablets) have emerged in medical literature; Quetiapine belongs to a series of neuroleptics known as atypical antipsychotics, which have become increasingly popular alternatives to typical antipsychotics such as haloperidol. Quetiapine HAS approvals for the treatment of schizophrenia and acute mania in bipolar disorder. It is also used off-label to treat other disorders, such as post-traumatic stress disorder, alcoholism, obsessive compulsive disorder, anxiety disorders, hallucinations in Parkinson's disease patients using ropinirole, and as a sedative for those with sleep disorders. The most common side effect is sedation, and is prescribed specifically for this effect in patients with sleep disorders. Seroquel will put the patient into a drowsy state, and will help the patient fall asleep. It is one of the most sedating of all anti psychotic drugs, rivaling even the most sedating older antipsychotics. Many prescriptions call for the entire dose to be taken before bedtime because of its sedative effects. Although quetiapine is approved by the FDA for the treatment of schizophrenia and bipolar disorder, it is frequently prescribed for off-label purposes including insomnia or the treatment of anxiety disorders. Due to its sedative side effects, reports of quetiapine abuse (sometimes by insufflating crushed tablets) have emerged in medical literature; for the same reason, abuse of other antipsychotics, such as chlorpromazine (Thorazine), may occur as well, but research related to the abuse of typical antipsychotics is limited. for the same reason, abuse of other antipsychotics, such as chlorpromazine (Thorazine), may occur as well, but research related to the abuse of typical antipsychotics is limited.
Compound Type
  • Amine
  • Antipsychotic Agent
  • Drug
  • Ether
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2-[2-(4-Dibenzo[b,F][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol
Quetiapina
Quetiapine fumarate
Quetiapine hemifumarate
Quetiapinum
Seroquel
Seroquel XR
Chemical FormulaC21H25N3O2S
Average Molecular Mass383.507 g/mol
Monoisotopic Mass383.167 g/mol
CAS Registry Number111974-69-7
IUPAC Name2-[2-(4-{2-thia-9-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,9,11,13-heptaen-10-yl}piperazin-1-yl)ethoxy]ethan-1-ol
Traditional Namequetiapine
SMILESOCCOCCN1CCN(CC1)C1=NC2=CC=CC=C2SC2=CC=CC=C12
InChI IdentifierInChI=1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2
InChI KeyInChIKey=URKOMYMAXPYINW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzothiazepines. Dibenzothiazepines are compounds containing a dibenzothiazepine moiety, which consists of two benzene connected by a thiazepine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazepines
Sub ClassDibenzothiazepines
Direct ParentDibenzothiazepines
Alternative Parents
Substituents
  • Dibenzothiazepine
  • Diarylthioether
  • Aryl thioether
  • N-alkylpiperazine
  • 1,4-diazinane
  • Piperazine
  • Benzenoid
  • Imidolactam
  • Tertiary amine
  • Tertiary aliphatic amine
  • Azacycle
  • Carboxylic acid amidine
  • Dialkyl ether
  • Ether
  • Amidine
  • Organic 1,3-dipolar compound
  • Thioether
  • Propargyl-type 1,3-dipolar organic compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Primary alcohol
  • Alcohol
  • Organic nitrogen compound
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceSolid (1).
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityModerate
LogP2.8
Predicted Properties
PropertyValueSource
Water Solubility0.04 g/LALOGPS
logP2.93ALOGPS
logP2.81ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)15.12ChemAxon
pKa (Strongest Basic)7.06ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area48.3 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity114.09 m³·mol⁻¹ChemAxon
Polarizability42.78 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, Positivesplash10-0007-9264000000-4758f7f7f4947282ccbb2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0fdo-9543200000-188eddba94dd2a57f9082017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-qTof , Negativesplash10-001i-0039000000-6e58caa07d6f7951f23e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-0089000000-b7b1c7d0bf6bb604c5cb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0uk9-1390000000-ce855b6e08dee583681b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0ul0-0092000000-b8ad82fb58fb41b6f4fa2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0019000000-380bdfab40abc4fe91042016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00e9-2019000000-9a9f0ea1ddcfe3e51fba2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-6942000000-82ff888287705b61f40d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1039000000-026ca51b770ab0fc287d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001l-2019000000-503cee9b3e7cc04ade6a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-08fu-9710000000-457979a8d0088bdeade22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0009000000-e07800842abb485794692021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000x-0019000000-f62857d5511d39f2c2012021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0w29-0191000000-5ce92b5e3a22486cc2f22021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-1009000000-74ca90c52d883a3f4f252021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4l-9027000000-059f5ab035332d4b8f682021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01p6-2192000000-1ea11b461430b2f762a12021-09-22View Spectrum
Toxicity Profile
Route of ExposureInhalation (MSDS, A308); ingestion (MSDS, A308); dermal (MSDS, A308) Rapidly and well absorbed.
Mechanism of ToxicityThe mechanism of action of quetiapine, as with other drugs used to treat schizophrenia, is unknown. However, it is thought that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) receptor antagonism. Although quetiapine is known to bind other receptors with similar affinity, only the dopamine D2 and serotonin 5HT2 receptor binding is responsible for quetiapine's therapeutic activity in schizophrenia.
MetabolismHepatic. The major metabolic pathways are sulfoxidation, mediated by cytochrome P450 3A4 (CYP3A4), and oxidation of the terminal alcohol to a carboxylic acid. The major sulfoxide metabolite of quetiapine is inactive. Quetiapine also undergoes hydroxylation of the dibenzothiazepine ring, O-deakylation, N-dealkylation, and phase II conjugation. The 7-hydroxy and 7-hydroxy- N-delakylated metabolites appear to be active, but are present in very low concentrations. Route of Elimination: Elimination of quetiapine is mainly via hepatic metabolism. Following a single oral dose of 14C-quetiapine, less than 1% of the administered dose was excreted as unchanged drug, indicating that quetiapine is highly metabolized. Approximately 73% and 20% of the dose was recovered in the urine and feces, respectively. Half Life: 6 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesQuetiapine is indicated for the treatment of schizophrenia, depressive episodes associated with bipolar disorder, acute manic episodes associated with bipolar I disorder, and maintenance treatment of bipolar I disorder (12).
Minimum Risk LevelNot Available
Health EffectsTachycardia, development of tardive dyskinesia, an incurable neurological disorder, and a neuroleptic malignant syndrome may result from use or overdose of Quetiapine (12).
SymptomsSymptoms of overdose include drowsiness and sedation, tachycardia, and hypotension.
TreatmentThere is no specific antidote. Treat quinidine-like cardiotoxic effects with bicarbonate. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. (11)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01224
HMDB IDHMDB05021
PubChem Compound ID5002
ChEMBL IDCHEMBL716
ChemSpider ID4827
KEGG IDC07397
UniProt IDNot Available
OMIM ID
ChEBI ID8707
BioCyc IDNot Available
CTD IDNot Available
Stitch IDQuetiapine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkQuetiapine
References
Synthesis Reference

DrugSyn.org

MSDSLink
General References
  1. 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 ]
  2. Mukaddes NM, Abali O: Quetiapine treatment of children and adolescents with Tourette's disorder. J Child Adolesc Psychopharmacol. 2003 Fall;13(3):295-9. [14642017 ]
  3. Dev V, Raniwalla J: Quetiapine: a review of its safety in the management of schizophrenia. Drug Saf. 2000 Oct;23(4):295-307. [11051217 ]
  4. Tallerico T, Novak G, Liu IS, Ulpian C, Seeman P: Schizophrenia: elevated mRNA for dopamine D2(Longer) receptors in frontal cortex. Brain Res Mol Brain Res. 2001 Mar 5;87(2):160-5. [11245917 ]
  5. Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. [18537577 ]
  6. Parker DR, McIntyre IM: Case studies of postmortem quetiapine: therapeutic or toxic concentrations? J Anal Toxicol. 2005 Jul-Aug;29(5):407-12. [16105271 ]
  7. Stip E, Fahim C, Mancini-Marie A, Bentaleb LA, Mensour B, Mendrek A, Beauregard M: Restoration of frontal activation during a treatment with quetiapine: an fMRI study of blunted affect in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jan;29(1):21-6. Epub 2004 Nov 5. [15610941 ]
  8. Langman LJ, Kaliciak HA, Carlyle S: Fatal overdoses associated with quetiapine. J Anal Toxicol. 2004 Sep;28(6):520-5. [15516308 ]
  9. Stephan PL, Jaquenoud Sirot E, Mueller B, Eap CB, Baumann P: Adverse drug reactions following nonresponse in a depressed patient with CYP2D6 deficiency and low CYP 3A4/5 activity. Pharmacopsychiatry. 2006 Jul;39(4):150-2. [16871470 ]
  10. Fahim C, Stip E, Mancini-Marie A, Gendron A, Mensour B, Beauregard M: Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment. J Clin Psychopharmacol. 2005 Aug;25(4):367-71. [16012281 ]
  11. ATSDR - Agency for Toxic Substances and Disease Registry (2007). Toxicological profile for 1,1,1-trichloroethane. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). [Link]
  12. Wikipedia. Quetiapine. Last Updated 8 August 2009. [Link]
  13. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
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
Inhibitory0.082 uMNot AvailableBindingDB 50095890
Inhibitory0.096 uMNot AvailableBindingDB 50095890
Inhibitory0.101 uMNot AvailableBindingDB 50095890
Inhibitory0.12 uMNot AvailableBindingDB 50095890
Inhibitory0.22 uMNot AvailableBindingDB 50095890
Inhibitory0.427 uMNot AvailableBindingDB 50095890
Inhibitory0.636 uMNot AvailableBindingDB 50095890
References
  1. 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 ]
  2. Goldstein JM: Quetiapine fumarate (Seroquel): a new atypical antipsychotic. Drugs Today (Barc). 1999 Mar;35(3):193-210. [12973385 ]
  3. McIntyre RS, Soczynska JK, Woldeyohannes HO, Alsuwaidan M, Konarski JZ: A preclinical and clinical rationale for quetiapine in mood syndromes. Expert Opin Pharmacother. 2007 Jun;8(9):1211-9. [17563257 ]
  4. Dev V, Raniwalla J: Quetiapine: a review of its safety in the management of schizophrenia. Drug Saf. 2000 Oct;23(4):295-307. [11051217 ]
  5. Leucht S, Pitschel-Walz G, Engel RR, Kissling W: Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry. 2002 Feb;159(2):180-90. [11823257 ]
  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. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
  8. Liegeois JF, Deville M, Dilly S, Lamy C, Mangin F, Resimont M, Tarazi FI: New pyridobenzoxazepine derivatives derived from 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13): chemical synthesis and pharmacological evaluation. J Med Chem. 2012 Feb 23;55(4):1572-82. doi: 10.1021/jm2013419. Epub 2012 Feb 13. [22268448 ]
  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. Kongsamut S, Kang J, Chen XL, Roehr J, Rampe D: A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs. Eur J Pharmacol. 2002 Aug 16;450(1):37-41. [12176106 ]
  12. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [8997630 ]
Target Details
2. 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
Inhibitory0.615 uMNot AvailableBindingDB 50095890
Inhibitory1.184 uMNot AvailableBindingDB 50095890
Inhibitory1.4 uMNot AvailableBindingDB 50095890
Inhibitory1.5 uMNot AvailableBindingDB 50095890
Inhibitory3.82 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. Stahl SM, Shayegan DK: The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice. J Clin Psychiatry. 2003;64 Suppl 19:6-12. [14728084 ]
  3. 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 ]
  4. 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 ]
  5. Li Z, Ichikawa J, Huang M, Prus AJ, Dai J, Meltzer HY: ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Psychopharmacology (Berl). 2005 Dec;183(2):144-53. Epub 2005 Nov 9. [16220333 ]
  6. 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 ]
  7. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [8997630 ]
  8. 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 ]
  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 ]
Target Details
3. 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
Inhibitory0.125 uMNot AvailableBindingDB 50095890
Inhibitory0.23 uMNot AvailableBindingDB 50095890
Inhibitory0.32 uMNot AvailableBindingDB 50095890
Inhibitory0.83 uMNot AvailableBindingDB 50095890
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Ichikawa J, Li Z, Dai J, Meltzer HY: Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: role of 5-HT1A receptor agonism. Brain Res. 2002 Nov 29;956(2):349-57. [12445705 ]
  3. McIntyre RS, Soczynska JK, Woldeyohannes HO, Alsuwaidan M, Konarski JZ: A preclinical and clinical rationale for quetiapine in mood syndromes. Expert Opin Pharmacother. 2007 Jun;8(9):1211-9. [17563257 ]
  4. Liegeois JF, Deville M, Dilly S, Lamy C, Mangin F, Resimont M, Tarazi FI: New pyridobenzoxazepine derivatives derived from 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13): chemical synthesis and pharmacological evaluation. J Med Chem. 2012 Feb 23;55(4):1572-82. doi: 10.1021/jm2013419. Epub 2012 Feb 13. [22268448 ]
  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. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
  7. 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
4. 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
Inhibitory0.069 uMNot AvailableBindingDB 50095890
Inhibitory0.18 uMNot AvailableBindingDB 50095890
Inhibitory0.31 uMNot AvailableBindingDB 50095890
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [11873706 ]
  3. Kapur S, Zipursky R, Jones C, Shammi CS, Remington G, Seeman P: A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy. Arch Gen Psychiatry. 2000 Jun;57(6):553-9. [10839333 ]
  4. Tallerico T, Novak G, Liu IS, Ulpian C, Seeman P: Schizophrenia: elevated mRNA for dopamine D2(Longer) receptors in frontal cortex. Brain Res Mol Brain Res. 2001 Mar 5;87(2):160-5. [11245917 ]
  5. 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 ]
  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 ]
  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
5. 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
Inhibitory0.056 uMNot AvailableBindingDB 50095890
Inhibitory0.1 uMNot AvailableBindingDB 50095890
Inhibitory0.12 uMNot AvailableBindingDB 50095890
Inhibitory0.135 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  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. Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL: Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1125-43. [14642972 ]
  6. 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
6. 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
Inhibitory0.39 uMNot AvailableBindingDB 50095890
Inhibitory1.277 uMNot AvailableBindingDB 50095890
Inhibitory1.3 uMNot AvailableBindingDB 50095890
Inhibitory4.24 uMNot AvailableBindingDB 50095890
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. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [8997630 ]
  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. 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
7. 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
Inhibitory1.6 uMNot AvailableBindingDB 50095890
Inhibitory2.2 uMNot AvailableBindingDB 50095890
Inhibitory>1 uMNot AvailableBindingDB 50095890
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. 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. Wermuth CG: Selective optimization of side activities: another way for drug discovery. J Med Chem. 2004 Mar 11;47(6):1303-14. [14998318 ]
  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. Liegeois JF, Deville M, Dilly S, Lamy C, Mangin F, Resimont M, Tarazi FI: New pyridobenzoxazepine derivatives derived from 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine (JL13): chemical synthesis and pharmacological evaluation. J Med Chem. 2012 Feb 23;55(4):1572-82. doi: 10.1021/jm2013419. Epub 2012 Feb 13. [22268448 ]
Target Details
8. 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
Inhibitory0.0022 uMNot AvailableBindingDB 50095890
Inhibitory0.0087 uMNot AvailableBindingDB 50095890
Inhibitory0.019 uMNot AvailableBindingDB 50095890
Inhibitory0.021 uMNot AvailableBindingDB 50095890
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
  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 ]
  5. 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
9. 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
Inhibitory0.32 uMNot AvailableBindingDB 50095890
Inhibitory0.34 uMNot AvailableBindingDB 50095890
Inhibitory0.65 uMNot AvailableBindingDB 50095890
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 ]
  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
10. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.705 uMNot AvailableBindingDB 50095890
Inhibitory1.32 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. 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 ]
  4. Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL: Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1125-43. [14642972 ]
Target Details
11. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.225 uMNot AvailableBindingDB 50095890
Inhibitory0.66 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. 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 ]
  4. Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL: Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1125-43. [14642972 ]
Target Details
12. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory5 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
Target Details
13. 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
Inhibitory2.23 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
Target Details
14. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.09 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
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
Inhibitory0.35 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
Target Details
16. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.63 uMNot AvailableBindingDB 50095890
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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 ]
  3. Bymaster FP, Felder CC, Tzavara E, Nomikos GG, Calligaro DO, Mckinzie DL: Muscarinic mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1125-43. [14642972 ]
Target Details
17. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.05 uMNot AvailableBindingDB 50095890
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. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
Target Details
18. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.25 uMNot AvailableBindingDB 50095890
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. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
Target Details
19. 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
Inhibitory1.4 uMNot AvailableBindingDB 50095890
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 ]
Target Details
20. 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. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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
21. 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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.513 uMNot AvailableBindingDB 50095890
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. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A: Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. [8997630 ]
Target Details
22. 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. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
  2. 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. 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
Inhibitory1 uMNot AvailableBindingDB 50095890
Inhibitory>18 uMNot AvailableBindingDB 50095890
References
  1. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
  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 ]
Target Details
24. 5-hydroxytryptamine receptor 1F
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:
HTR1F
Uniprot ID:
P30939
Molecular Weight:
41708.505 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.24 uMNot AvailableBindingDB 50095890
References
  1. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
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. Goudie AJ, Smith JA, Taylor A, Taylor MA, Tricklebank MD: Discriminative stimulus properties of the atypical neuroleptic clozapine in rats: tests with subtype selective receptor ligands. Behav Pharmacol. 1998 Dec;9(8):699-710. [9890260 ]
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 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
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
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-1D adrenergic receptor
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Richelson E, Souder T: Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 2000 Nov 24;68(1):29-39. [11132243 ]
Target Details
30. Beta-1 adrenergic receptor
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.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory5 uMNot AvailableBindingDB 50095890
References
  1. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]