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Record Information
Version2.0
Creation Date2009-07-21 20:27:01 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2806
Identification
Common NameChlorpromazine
ClassSmall Molecule
DescriptionThe prototypical phenothiazine antipsychotic drug. Like the other drugs in this class, chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.
Compound Type
  • Amine
  • Antiemetic
  • Antipsychotic Agent
  • Dopamine Antagonist
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Organochloride
  • Phenothiazine
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-(2-chloro-10H-Phenothiazin-10-yl)-N,N-dimethyl-1-propanamine
3-(2-Chlorophenothiazin-10-yl)-N,N-dimethyl-propan-1-amine
Aminazine
Chlorderazin
Chloropromazine
Chlorpromados
Chlorpromazinum
Clorpromazina
Contomin
CPZ
Largactil
N-(3-Dimethylaminopropyl)-3-chlorophenothiazine
Thorazine
Chemical FormulaC17H19ClN2S
Average Molecular Mass318.864 g/mol
Monoisotopic Mass318.096 g/mol
CAS Registry Number50-53-3
IUPAC Name[3-(2-chloro-10H-phenothiazin-10-yl)propyl]dimethylamine
Traditional Namechlorpromazine
SMILESCN(C)CCCN1C2=CC=CC=C2SC2=C1C=C(Cl)C=C2
InChI IdentifierInChI=1S/C17H19ClN2S/c1-19(2)10-5-11-20-14-6-3-4-7-16(14)21-17-9-8-13(18)12-15(17)20/h3-4,6-9,12H,5,10-11H2,1-2H3
InChI KeyInChIKey=ZPEIMTDSQAKGNT-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Aryl thioether
  • Tertiary aliphatic/aromatic amine
  • Para-thiazine
  • Aryl chloride
  • Aryl halide
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Thioether
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point177-178°C
Boiling Point200-205°C at 8.00E-01 mm Hg
Solubility2.55 mg/L (at 24°C)
LogP5.41
Predicted Properties
PropertyValueSource
Water Solubility0.0042 g/LALOGPS
logP5.18ALOGPS
logP4.54ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity93.76 m³·mol⁻¹ChemAxon
Polarizability35.1 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4r-9053000000-9e1cc1d4fc6be5bc73b8JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-014i-2019000000-54e008f9fc11d7f45b68JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-000i-9070000000-9bbe6c5123c891b9489bJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4r-9053000000-9e1cc1d4fc6be5bc73b8JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-014i-2019000000-54e008f9fc11d7f45b68JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-000i-9070000000-9bbe6c5123c891b9489bJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4j-9161000000-fb3a39cba2075363c833JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0019000000-0028b3984b4c35e44defJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0090000000-800bf68c2158920c3f30JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03dj-0090000000-649e773296a3ecec2b04JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0190000000-7404aac4e28621b4f60aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-01b9-0019000000-993566c51e802e754da2JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-1029000000-7e34879597957c9ee39fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01bi-9076000000-5e7e6025c08ddac427f2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-059f-9320000000-af8b418201e78097c537JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0019000000-86aa9bde1ce82c180318JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0aor-0393000000-613da71e073b4dd78512JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001j-3890000000-a4243a809dea08eb0af6JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0a4i-9231000000-ed14fee152701eacf689JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral, Intravenous. Readily absorbed from the GI tract. Bioavailability varies due to first-pass metabolism by the liver.
Mechanism of ToxicityChlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use).
MetabolismExtensively metabolized in the liver and kidneys. It is extensively metabolized by cytochrome P450 isozymes CYP2D6 (major pathway), CYP1A2 and CYP3A4. Approximately 10 to 12 major metabolite have been identified. Hydroxylation at positions 3 and 7 of the phenothiazine nucleus and the N-dimethylaminopropyl side chain undergoes demethylation and is also metabolized to an N-oxide. In urine, 20% of chlopromazine and its metabolites are excreted unconjugated in the urine as unchanged drug, demonomethylchlorpromazine, dedimethylchlorpromazine, their sulfoxide metabolites, and chlorpromazine-N-oxide. The remaining 80% consists of conjugated metabolites, principally O-glucuronides and small amounts of ethereal sulfates of the mono- and dihydroxy-derivatives of chlorpromazine and their sulfoxide metabolites. The major metabolites are the monoglucuronide of N-dedimethylchlorpromazine and 7-hydroxychlorpromazine. Approximately 37% of the administered dose of chlorpromazine is excreted in urine. Route of Elimination: Kidneys, ~ 37% excreted in urine Half Life: ~ 30 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of schizophrenia, control nausea and vomiting, For relief of restlessness and apprehension before surgery, adjunct in the treatment of tetanus, control the manifestations of the manic type of manic-depressive illness.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsAgitation, coma, convulsions, difficulty breathing, difficulty swallowing, dry mouth, extreme sleepiness, fever, intestinal blockage, irregular heart rate, low blood pressure, restlessness
TreatmentTreatment is essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage. Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus. Extrapyramidal symptoms may be treated with anti-parkinsonism drugs, barbiturates, or Benadryl. Care should be taken to avoid increasing respiratory depression. If administration of a stimulant is desirable, amphetamine, dextroamphetamine, or caffeine with sodium benzoate is recommended. Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided. If hypotension occurs, the standard measures for managing circulatory shock should be initiated. If it is desirable to administer a vasoconstrictor, Levophed and Neo-Synephrine are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause a further lowering of blood pressure. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00477
HMDB IDHMDB14620
PubChem Compound ID2726
ChEMBL IDCHEMBL71
ChemSpider ID2625
KEGG IDC06906
UniProt IDNot Available
OMIM ID
ChEBI ID3647
BioCyc IDNot Available
CTD IDNot Available
Stitch IDChlorpromazine
PDB IDZ80
ACToR IDNot Available
Wikipedia LinkChlorpromazine
References
Synthesis Reference

Charpentier, P.; U S . Patent 2,645,640; July 14, 1953; assigned to Societe des Usines Chimiques Rhone-Poulenc, France.

MSDSLink
General References
  1. Leucht S, Wahlbeck K, Hamann J, Kissling W: New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet. 2003 May 10;361(9369):1581-9. [12747876 ]
  2. Drugs.com [Link]
  3. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0012 uMNot AvailableBindingDB 50001888
Inhibitory0.00406 uMNot AvailableBindingDB 50001888
Inhibitory0.008 uMNot AvailableBindingDB 50001888
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. Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. [11103886 ]
  4. Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. [15694263 ]
  5. Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. [16867246 ]
  6. Clark AH, McCorvy JD, Conley JM, Williams WK, Bekkam M, Watts VJ, Nichols DE: Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D(3) receptor-selective full agonist ligand. Bioorg Med Chem. 2012 Nov 1;20(21):6366-74. doi: 10.1016/j.bmc.2012.08.058. Epub 2012 Sep 8. [23018094 ]
  7. von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
  8. Cueva JP, Giorgioni G, Grubbs RA, Chemel BR, Watts VJ, Nichols DE: trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist. J Med Chem. 2006 Nov 16;49(23):6848-57. [17154515 ]
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
Inhibitory0.003 uMNot AvailableBindingDB 50001888
Inhibitory0.00425 uMNot AvailableBindingDB 50001888
Inhibitory0.009 uMNot AvailableBindingDB 50001888
References
  1. Hals PA, Hall H, Dahl SG: Muscarinic cholinergic and histamine H1 receptor binding of phenothiazine drug metabolites. Life Sci. 1988;43(5):405-12. [2899826 ]
  2. Church MK, Young KD: The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine. Br J Pharmacol. 1983 Apr;78(4):671-9. [6189542 ]
  3. Johnson HG, Miller MD: Inhibition of histamine release and ionophore-induced calcium flux in rat mast cells by lidocaine and chlorpromazine. Agents Actions. 1979 Aug;9(3):239-43. [91313 ]
  4. Palmer GC, Wagner HR, Palmer SJ, Manian AA: Histamine-, norepinephrine-, and dopamine-sensitive central adenylate cyclases: effects of chlorpromazine derivatives and butaclamol. Arch Int Pharmacodyn Ther. 1978 Jun;233(2):314-25. [687395 ]
  5. Ruffolo RR, Patil PN: Kinetics of blockade of different receptors by chlorpromazine in rabbit stomach strips. Eur J Pharmacol. 1978 Mar 15;48(2):151-7. [25190 ]
  6. Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]
  7. von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
  8. Richelson E, Nelson A: Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204. [6149136 ]
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
IC501.47 uMNot AvailableBindingDB 50001888
IC501.479 uMNot AvailableBindingDB 50001888
IC501.47911 uMNot AvailableBindingDB 50001888
References
  1. Thomas D, Wu K, Kathofer S, Katus HA, Schoels W, Kiehn J, Karle CA: The antipsychotic drug chlorpromazine inhibits HERG potassium channels. Br J Pharmacol. 2003 Jun;139(3):567-74. [12788816 ]
  2. Cavalli A, Poluzzi E, De Ponti F, Recanatini M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J Med Chem. 2002 Aug 29;45(18):3844-53. [12190308 ]
  3. 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 ]
  4. Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
  5. 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 ]
  6. 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 ]
  7. Ermondi G, Visentin S, Caron G: GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers. Eur J Med Chem. 2009 May;44(5):1926-32. doi: 10.1016/j.ejmech.2008.11.009. Epub 2008 Nov 28. [19110341 ]
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
Inhibitory0.673 uMNot AvailableBindingDB 50001888
Inhibitory3.115 uMNot AvailableBindingDB 50001888
References
  1. Cosi C, Koek W: Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. Eur J Pharmacol. 2001 Dec 14;433(1):55-62. [11755134 ]
  2. Newman-Tancredi A, Gavaudan S, Conte C, Chaput C, Touzard M, Verriele L, Audinot V, Millan MJ: Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study. Eur J Pharmacol. 1998 Aug 21;355(2-3):245-56. [9760039 ]
  3. Lin CH, Haadsma-Svensson SR, Lahti RA, McCall RB, Piercey MF, Schreur PJ, Von Voigtlander PF, Smith MW, Chidester CG: Centrally acting serotonergic and dopaminergic agents. 1. Synthesis and structure-activity relationships of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives. J Med Chem. 1993 Apr 16;36(8):1053-68. [8097537 ]
  4. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
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
Inhibitory0.044 uMNot AvailableBindingDB 50001888
Inhibitory0.073 uMNot AvailableBindingDB 50001888
Inhibitory0.096 uMNot AvailableBindingDB 50001888
References
  1. Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. [7918347 ]
  2. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
  3. Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB: Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9. [1826762 ]
  4. von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
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
Inhibitory0.003 uMNot AvailableBindingDB 50001888
Inhibitory0.0038 uMNot AvailableBindingDB 50001888
Inhibitory0.0069 uMNot AvailableBindingDB 50001888
References
  1. Freedman SB, Patel S, Marwood R, Emms F, Seabrook GR, Knowles MR, McAllister G: Expression and pharmacological characterization of the human D3 dopamine receptor. J Pharmacol Exp Ther. 1994 Jan;268(1):417-26. [8301582 ]
  2. Varady J, Wu X, Fang X, Min J, Hu Z, Levant B, Wang S: Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor: discovery of novel and potent D3 ligands through a hybrid pharmacophore- and structure-based database searching approach. J Med Chem. 2003 Oct 9;46(21):4377-92. [14521403 ]
  3. Clark AH, McCorvy JD, Conley JM, Williams WK, Bekkam M, Watts VJ, Nichols DE: Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D(3) receptor-selective full agonist ligand. Bioorg Med Chem. 2012 Nov 1;20(21):6366-74. doi: 10.1016/j.bmc.2012.08.058. Epub 2012 Sep 8. [23018094 ]
  4. von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
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
Inhibitory0.07 uMNot AvailableBindingDB 50001888
Inhibitory0.15 uMNot AvailableBindingDB 50001888
Inhibitory0.215 uMNot AvailableBindingDB 50001888
References
  1. Richelson E, Nelson A: Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204. [6149136 ]
  2. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
  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 ]
  4. Kovacs I, Yamamura HI, Waite SL, Varga EV, Roeske WR: Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7. [9454790 ]
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation54.954 uMNot AvailableBindingDB 50001888
References
  1. Rukhadze MD, Bezarashvili GS, Sidamonidze NS, Tsagareli SK: Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments. Biomed Chromatogr. 2001 Oct;15(6):365-73. [11559920 ]
  2. Silva D, Cortez CM, Louro SR: Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Braz J Med Biol Res. 2004 Jul;37(7):963-8. Epub 2004 Jun 22. [15264002 ]
  3. Kitamura K, Omran AA, Nagata C, Kamijima Y, Tanaka R, Takegami S, Kitade T: Effects of inorganic ions on the binding of triflupromazine and chlorpromazine to bovine serum albumin studied by spectrometric methods. Chem Pharm Bull (Tokyo). 2006 Jul;54(7):972-6. [16819214 ]
  4. Lazaro E, Lowe PJ, Briand X, Faller B: New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin. J Med Chem. 2008 Apr 10;51(7):2009-17. doi: 10.1021/jm7012826. Epub 2008 Mar 19. [18348514 ]
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
Inhibitory0.0018 uMNot AvailableBindingDB 50001888
References
  1. Kusumi I, Takahashi Y, Suzuki K, Kameda K, Koyama T: Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain. J Neural Transm. 2000;107(3):295-302. [10821438 ]
  2. Yamada J, Sugimoto Y, Horisaka K: Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice. Biol Pharm Bull. 1995 Nov;18(11):1580-3. [8593484 ]
  3. Seeman P, Tallerico T: Antipsychotic drugs which elicit little or no parkinsonism bind more loosely than dopamine to brain D2 receptors, yet occupy high levels of these receptors. Mol Psychiatry. 1998 Mar;3(2):123-34. [9577836 ]
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
Inhibitory0.004 uMNot AvailableBindingDB 50001888
Inhibitory0.019 uMNot AvailableBindingDB 50001888
References
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [7908055 ]
  2. Glennon RA: Higher-end serotonin receptors: 5-HT(5), 5-HT(6), and 5-HT(7). J Med Chem. 2003 Jul 3;46(14):2795-812. [12825922 ]
  3. Kohen R, Metcalf MA, Khan N, Druck T, Huebner K, Lachowicz JE, Meltzer HY, Sibley DR, Roth BL, Hamblin MW: Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor. J Neurochem. 1996 Jan;66(1):47-56. [8522988 ]
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
Inhibitory0.078 uMNot AvailableBindingDB 50001888
Inhibitory0.558 uMNot AvailableBindingDB 50001888
Inhibitory0.75 uMNot AvailableBindingDB 50001888
References
  1. Bylund DB, Blaxall HS, Iversen LJ, Caron MG, Lefkowitz RJ, Lomasney JW: Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol. 1992 Jul;42(1):1-5. [1353247 ]
  2. Naselsky DP, Ashton D, Ruffolo RR Jr, Hieble JP: Rabbit alpha2-adrenoceptors: both platelets and adipocytes have alpha2A-pharmacology. J Pharmacol Exp Ther. 2001 Jul;298(1):219-25. [11408545 ]
  3. Richelson E, Nelson A: Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol. 1984 Aug 17;103(3-4):197-204. [6149136 ]
General Function:
Titin binding
Specific Function:
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis.
Gene Name:
CALM1
Uniprot ID:
P0DP23
Molecular Weight:
16837.47 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory19.28 uMNot AvailableBindingDB 50001888
IC507.26 uMNot AvailableBindingDB 50001888
IC5010.3 uMNot AvailableBindingDB 50001888
References
  1. Marshak DR, Lukas TJ, Watterson DM: Drug-protein interactions: binding of chlorpromazine to calmodulin, calmodulin fragments, and related calcium binding proteins. Biochemistry. 1985 Jan 1;24(1):144-50. [2986673 ]
  2. Figueroa M, Gonzalez Mdel C, Rodriguez-Sotres R, Sosa-Peinado A, Gonzalez-Andrade M, Cerda-Garcia-Rojas CM, Mata R: Calmodulin inhibitors from the fungus Emericella sp. Bioorg Med Chem. 2009 Mar 15;17(6):2167-74. doi: 10.1016/j.bmc.2008.10.079. Epub 2008 Nov 5. [19013822 ]
  3. Reyes-Ramirez A, Leyte-Lugo M, Figueroa M, Serrano-Alba T, Gonzalez-Andrade M, Mata R: Synthesis, biological evaluation, and docking studies of gigantol analogs as calmodulin inhibitors. Eur J Med Chem. 2011 Jul;46(7):2699-708. doi: 10.1016/j.ejmech.2011.03.057. Epub 2011 Apr 3. [21514702 ]
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
Inhibitory0.133 uMNot AvailableBindingDB 50001888
Inhibitory0.172 uMNot AvailableBindingDB 50001888
References
  1. Seeman P, Van Tol HH: Dopamine receptor pharmacology. Curr Opin Neurol Neurosurg. 1993 Aug;6(4):602-8. [8104554 ]
  2. Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR, Torchia J, Van Tol HH, Niznik HB: Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614-9. [1826762 ]
  3. von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
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
Inhibitory0.025 uMNot AvailableBindingDB 50001888
References
  1. Davies MA, Compton-Toth BA, Hufeisen SJ, Meltzer HY, Roth BL: The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions? Psychopharmacology (Berl). 2005 Apr;178(4):451-60. Epub 2004 Oct 13. [15765260 ]
  2. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
  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 ]
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
Inhibitory0.067 uMNot AvailableBindingDB 50001888
References
  1. Davies MA, Compton-Toth BA, Hufeisen SJ, Meltzer HY, Roth BL: The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M1 agonism a pre-requisite for mimicking clozapine's actions? Psychopharmacology (Berl). 2005 Apr;178(4):451-60. Epub 2004 Oct 13. [15765260 ]
  2. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
  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 ]
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
Inhibitory0.027 uMNot AvailableBindingDB 50001888
References
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [7908055 ]
  2. Lebar MD, Hahn KN, Mutka T, Maignan P, McClintock JB, Amsler CD, van Olphen A, Kyle DE, Baker BJ: CNS and antimalarial activity of synthetic meridianin and psammopemmin analogs. Bioorg Med Chem. 2011 Oct 1;19(19):5756-62. doi: 10.1016/j.bmc.2011.08.033. Epub 2011 Aug 22. [21907583 ]
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
Inhibitory0.027 uMNot AvailableBindingDB 50001888
References
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [7908055 ]
  2. Lebar MD, Hahn KN, Mutka T, Maignan P, McClintock JB, Amsler CD, van Olphen A, Kyle DE, Baker BJ: CNS and antimalarial activity of synthetic meridianin and psammopemmin analogs. Bioorg Med Chem. 2011 Oct 1;19(19):5756-62. doi: 10.1016/j.bmc.2011.08.033. Epub 2011 Aug 22. [21907583 ]
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
Inhibitory0.04 uMNot AvailableBindingDB 50001888
References
  1. Bolden C, Cusack B, Richelson E: Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J Pharmacol Exp Ther. 1992 Feb;260(2):576-80. [1346637 ]
  2. 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 ]
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC504.3 uMNot AvailableBindingDB 50001888
IC5027 uMNot AvailableBindingDB 50001888
References
  1. Bednarczyk D, Ekins S, Wikel JH, Wright SH: Influence of molecular structure on substrate binding to the human organic cation transporter, hOCT1. Mol Pharmacol. 2003 Mar;63(3):489-98. [12606755 ]
  2. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [18788725 ]
20. 5-hydroxytryptamine 2 receptor (Protein Group)
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.
Included Proteins:
P28223 , P41595 , P28335
References
  1. Roth BL, Craigo SC, Choudhary MS, Uluer A, Monsma FJ Jr, Shen Y, Meltzer HY, Sibley DR: Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10. [7908055 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.052 uMNot AvailableBindingDB 50001888
References
  1. Hajjo R, Grulke CM, Golbraikh A, Setola V, Huang XP, Roth BL, Tropsha A: Development, validation, and use of quantitative structure-activity relationship models of 5-hydroxytryptamine (2B) receptor ligands to identify novel receptor binders and putative valvulopathic compounds among common drugs. J Med Chem. 2010 Nov 11;53(21):7573-86. doi: 10.1021/jm100600y. [20958049 ]
General Function:
Xanthine dehydrogenase activity
Specific Function:
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.
Gene Name:
AOX1
Uniprot ID:
Q06278
Molecular Weight:
147916.735 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.3 uMNot AvailableBindingDB 50001888
IC500.57 uMNot AvailableBindingDB 50001888
References
  1. Pryde DC, Dalvie D, Hu Q, Jones P, Obach RS, Tran TD: Aldehyde oxidase: an enzyme of emerging importance in drug discovery. J Med Chem. 2010 Dec 23;53(24):8441-60. doi: 10.1021/jm100888d. Epub 2010 Sep 20. [20853847 ]
23. Alpha-1 adrenergic receptors (Protein Group)
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.
Included Proteins:
P35348 , P35368 , P25100
References
  1. Huerta-Bahena J, Villalobos-Molina R, Garcia-Sainz JA: Trifluoperazine and chlorpromazine antagonize alpha 1- but not alpha2- adrenergic effects. Mol Pharmacol. 1983 Jan;23(1):67-70. [6135146 ]
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [8946472 ]
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM2
Uniprot ID:
P19652
Molecular Weight:
23602.43 Da
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [8946472 ]
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. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [15695070 ]
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. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [15695070 ]
28. Alpha-2 adrenergic receptors (Protein Group)
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.
Included Proteins:
P08913 , P18089 , P18825
References
  1. Bylund DB, Ray-Prenger C, Murphy TJ: Alpha-2A and alpha-2B adrenergic receptor subtypes: antagonist binding in tissues and cell lines containing only one subtype. J Pharmacol Exp Ther. 1988 May;245(2):600-7. [2835476 ]
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
Inhibitory0.0048 uMNot AvailableBindingDB 50001888
References
  1. Bylund DB, Blaxall HS, Iversen LJ, Caron MG, Lefkowitz RJ, Lomasney JW: Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol. 1992 Jul;42(1):1-5. [1353247 ]
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
Inhibitory0.041 uMNot AvailableBindingDB 50001888
References
  1. Bylund DB, Blaxall HS, Iversen LJ, Caron MG, Lefkowitz RJ, Lomasney JW: Pharmacological characteristics of alpha 2-adrenergic receptors: comparison of pharmacologically defined subtypes with subtypes identified by molecular cloning. Mol Pharmacol. 1992 Jul;42(1):1-5. [1353247 ]
General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular Weight:
146405.83 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5030.9 uMNot AvailableBindingDB 50001888
IC5033.5 uMNot AvailableBindingDB 50001888
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [12739759 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory7 uMNot AvailableBindingDB 50001888
References
  1. Strobl GR, von Kruedener S, Stockigt J, Guengerich FP, Wolff T: Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies. J Med Chem. 1993 Apr 30;36(9):1136-45. [8487254 ]
33. 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. Seeman P, Van Tol HH: Dopamine receptor pharmacology. Curr Opin Neurol Neurosurg. 1993 Aug;6(4):602-8. [8104554 ]
General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
References
  1. Roth BL, Tandra S, Burgess LH, Sibley DR, Meltzer HY: D4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs. Psychopharmacology (Berl). 1995 Aug;120(3):365-8. [8524985 ]
General Function:
Histamine receptor activity
Specific Function:
The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization.
Gene Name:
HRH3
Uniprot ID:
Q9Y5N1
Molecular Weight:
48670.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>1 uMNot AvailableBindingDB 50001888
References
  1. von Coburg Y, Kottke T, Weizel L, Ligneau X, Stark H: Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg Med Chem Lett. 2009 Jan 15;19(2):538-42. doi: 10.1016/j.bmcl.2008.09.012. Epub 2008 Sep 7. [19091563 ]
General Function:
Histamine receptor activity
Specific Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
Gene Name:
HRH4
Uniprot ID:
Q9H3N8
Molecular Weight:
44495.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0502 uMNot AvailableBindingDB 50001888
References
  1. Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF: Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33. [11179435 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.6 uMNot AvailableBindingDB 50001888
Inhibitory12.2 uMNot AvailableBindingDB 50001888
References
  1. Pajeva IK, Wiese M: Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J Med Chem. 2002 Dec 19;45(26):5671-86. [12477351 ]
General Function:
Voltage-gated proton channel activity
Specific Function:
NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain.
Gene Name:
NOX1
Uniprot ID:
Q9Y5S8
Molecular Weight:
64870.455 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>17 uMNot AvailableBindingDB 50001888
References
  1. 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 ]
General Function:
Sphingomyelin phosphodiesterase activity
Specific Function:
Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic activity.
Gene Name:
SMPD1
Uniprot ID:
P17405
Molecular Weight:
69751.3 Da
References
  1. Yoshida Y, Arimoto K, Sato M, Sakuragawa N, Arima M, Satoyoshi E: Reduction of acid sphingomyelinase activity in human fibroblasts induced by AY-9944 and other cationic amphiphilic drugs. J Biochem. 1985 Dec;98(6):1669-79. [2419314 ]
40. alpha1-acid glycoprotein (Protein Group)
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Included Proteins:
P02763 , P19652
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [8946472 ]