Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:27:23 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2856
Identification
Common NameSumatriptan
ClassSmall Molecule
DescriptionOftentimes, serotonin levels in the brain become extremely erratic before the onset of a migraine. In an attempt to stabilize this, sumatriptan is administered to help aid in leveling the serotonin levels in the brain. Sumatriptan is structurally similar to serotonin, and is a 5-HT (5-HT1D) agonist, which is one of the receptors that serotonin binds to. The specific receptor subtype it activates is present in the cranial and basilar arteries. Activation of these receptors causes vasoconstriction of those dilated arteries. Sumatriptan is also shown to decrease the activity of the trigeminal nerve. Sumatriptan is a triptan drug including a sulfonamide group structurally similar to serotonin, and is a 5-HT (5-HT1D) agonist, which is one of the receptors that serotonin binds to. Oftentimes, serotonin levels in the brain become extremely erratic before the onset of a migraine. In an attempt to stabilize this, sumatriptan is administered to help aid in leveling the serotonin levels in the brain. A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. Sumatriptan (Imitrex, Imigran, Imigran Recovery) is a triptan drug including a sulfonamide group which was originally developed by Glaxo for the treatment of migraine headaches.
Compound Type
  • Amide
  • Amine
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Selective Serotonin Agonist
  • Serotonin 5-HT1 Receptor Agonist
  • Serotonin Agonist
  • Serotonin Antagonist
  • Serotonin Receptor Agonist
  • Synthetic Compound
  • Vasoconstrictor Agent
Chemical Structure
Thumb
Synonyms
Synonym
(3-[2-(dimethylamino)Ethyl]-1H-indol-5-yl)-N-methylmethanesulfonamide
1-[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]-N-methyl-methanesulfonamide
3-(2-(dimethylamino)Ethyl)-N-methyl-1H-indole-5-methanesulfonamide
3-[2-(dimethylamino)Ethyl]-N-methylindole-5-methanesulfonamide
Adracon
ALSUMA
Altaxa
Apigrane
Boots Pharmacy Migraine Relief
Cinie
Frimig
Illument
Imigen
Imigran
Imigran mite
Imigran Radis
Imigran Recovery
Imigrane
Imitrex
Imitrex Oral
Migralgin
Migraneitor
Nazdav
NP101
Sapphirex
Sumatran
Sumatriptan Succinate
Sumatriptanum
Sumax
Suminat
triptan
Youshu
ZECUITY
Chemical FormulaC14H21N3O2S
Average Molecular Mass295.400 g/mol
Monoisotopic Mass295.135 g/mol
CAS Registry Number103628-46-2
IUPAC Name1-{3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}-N-methylmethanesulfonamide
Traditional Namesumatriptan
SMILESCNS(=O)(=O)CC1=CC2=C(NC=C2CCN(C)C)C=C1
InChI IdentifierInChI=1S/C14H21N3O2S/c1-15-20(18,19)10-11-4-5-14-13(8-11)12(9-16-14)6-7-17(2)3/h4-5,8-9,15-16H,6-7,10H2,1-3H3
InChI KeyInChIKey=KQKPFRSPSRPDEB-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tryptamines and derivatives. Tryptamines and derivatives are compounds containing the tryptamine backbone, which is structurally characterized by an indole ring substituted at the 3-position by an ethanamine.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassTryptamines and derivatives
Direct ParentTryptamines and derivatives
Alternative Parents
Substituents
  • Tryptamine
  • 3-alkylindole
  • Indole
  • Aralkylamine
  • Substituted pyrrole
  • Organic sulfonic acid amide
  • Benzenoid
  • Organosulfonic acid amide
  • Pyrrole
  • Organic sulfonic acid or derivatives
  • Heteroaromatic compound
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Brain
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point169-171°C
Boiling PointNot Available
Solubility21.4 mg/ml
LogP0.93
Predicted Properties
PropertyValueSource
Water Solubility0.13 g/LALOGPS
logP1.17ALOGPS
logP0.74ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)11.24ChemAxon
pKa (Strongest Basic)9.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area65.2 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity82.08 m³·mol⁻¹ChemAxon
Polarizability32.31 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0zfr-7390000000-5809ad2270f77ffcec79View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03di-0190000000-c12ee3ac5f29c3420996View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-2910000000-8769dc29dcac8fede7d1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0390000000-cdddf05865e6d570c337View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-2910000000-8769dc29dcac8fede7d1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000t-0090000000-42a6041e68fbb33f3c3cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uxr-1290000000-18f63d6714d369042cedView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a59-1910000000-b311f02f2295ff294573View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-3090000000-23dacc0baf4eac1e818aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00mo-9280000000-45a6f0dbb82744e4f102View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01r6-9120000000-ca48d4e064a2f6323651View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a4i-9400000000-93cc7dc7e521f98aa292View in MoNA
Toxicity Profile
Route of ExposureSubcutaneous, Oral, Nasal, Transdermal
Mechanism of ToxicityThe 5-HT1B and 5-HT1D receptors function as autoreceptors, which inhibit the firing of serotonin neurons and a reduction in the synthesis and release of serotonin upon activation. After sumatriptan binds to these receptors, adenylate cyclase activity is inhibited via regulatory G proteins, incrases intracellular calcium, and affects other intracellular events. This results in vasoconstriction and inhibtion of sensory nociceptive (trigeminal) nerve firing and vasoactive neuropeptide release. Sumatriptan stimulates 5-HT receptors of the 1D subtype, most likely presynaptic receptors, resulting in selective vasoconstriction of inflamed and dilated cranial blood vessels in the carotid circulation. Sumatriptan also blocks the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater during migraine and may inhibit the release of inflammatory mediators from the trigeminal nerve.
MetabolismHepatic. In vitro studies with human microsomes suggest that sumatriptan is metabolized by monoamine oxidase (MAO), predominantly the A isoenzyme. Route of Elimination: Only 3% of the dose is excreted in the urine as unchanged sumatriptan; 42% of the dose is excreted as the major metabolite, the indole acetic acid analogue of sumatriptan. Half Life: 2.5 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 migraine attacks with or without aura.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00669
HMDB IDHMDB05037
PubChem Compound ID5358
ChEMBL IDCHEMBL128
ChemSpider ID5165
KEGG IDC07319
UniProt IDNot Available
OMIM ID
ChEBI ID10650
BioCyc IDNot Available
CTD IDNot Available
Stitch IDSumatriptan
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkSumatriptan
References
Synthesis Reference

Rajeev Mathur, T. Kumar, Sunilendu Roy, Rajiv Malik, “Taste masked sumatriptan tablets and processes for their preparation.” U.S. Patent US20060233875, issued October 19, 2006.

MSDSLink
General References
  1. Nikai T, Basbaum AI, Ahn AH: Profound reduction of somatic and visceral pain in mice by intrathecal administration of the anti-migraine drug, sumatriptan. Pain. 2008 Oct 31;139(3):533-40. doi: 10.1016/j.pain.2008.06.002. Epub 2008 Aug 23. [18723285 ]
  2. Pascual J, del Arco C, Romon T, del Olmo E, Castro E, Pazos A: Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem human brain. Cephalalgia. 1996 Aug;16(5):317-22. [8869766 ]
  3. Castro ME, Pascual J, Romon T, del Arco C, del Olmo E, Pazos A: Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord. Neuropharmacology. 1997 Apr-May;36(4-5):535-42. [9225278 ]
  4. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
Inhibitory0.0231 uMNot AvailableBindingDB 50005835
Inhibitory0.024 uMNot AvailableBindingDB 50005835
Inhibitory0.02511 uMNot AvailableBindingDB 50005835
Inhibitory0.028 uMNot AvailableBindingDB 50005835
Inhibitory0.036 uMNot AvailableBindingDB 50005835
Inhibitory0.0479 uMNot AvailableBindingDB 50005835
Inhibitory0.06 uMNot AvailableBindingDB 50005835
Inhibitory0.06165 uMNot AvailableBindingDB 50005835
Inhibitory0.0012 uMNot AvailableBindingDB 50005835
Inhibitory0.00199 uMNot AvailableBindingDB 50005835
Inhibitory0.002 uMNot AvailableBindingDB 50005835
Inhibitory0.0034 uMNot AvailableBindingDB 50005835
Inhibitory0.0055 uMNot AvailableBindingDB 50005835
Inhibitory0.0064 uMNot AvailableBindingDB 50005835
Inhibitory0.0077 uMNot AvailableBindingDB 50005835
Inhibitory0.00776 uMNot AvailableBindingDB 50005835
Inhibitory0.0091 uMNot AvailableBindingDB 50005835
Inhibitory0.00933 uMNot AvailableBindingDB 50005835
Inhibitory0.0096 uMNot AvailableBindingDB 50005835
Inhibitory0.01 uMNot AvailableBindingDB 50005835
Inhibitory0.01096 uMNot AvailableBindingDB 50005835
Inhibitory0.0191 uMNot AvailableBindingDB 50005835
Inhibitory0.022 uMNot AvailableBindingDB 50005835
Inhibitory0.023 uMNot AvailableBindingDB 50005835
IC500.01 uMNot AvailableBindingDB 50005835
IC500.011 uMNot AvailableBindingDB 50005835
IC500.016 uMNot AvailableBindingDB 50005835
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Dupuis DS, Perez M, Halazy S, Colpaert FC, Pauwels PJ: Magnitude of 5-HT1B and 5-HT1A receptor activation in guinea-pig and rat brain: evidence from sumatriptan dimer-mediated [35S]GTPgammaS binding responses. Brain Res Mol Brain Res. 1999 Apr 6;67(1):107-23. [10101238 ]
  3. Mitsikostas DD, Sanchez del Rio M, Moskowitz MA, Waeber C: Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis. Eur J Pharmacol. 1999 Mar 26;369(3):271-7. [10225363 ]
  4. Cohen ML, Schenck KW, Hemrick-Luecke SH: 5-Hydroxytryptamine(1A) receptor activation enhances norepinephrine release from nerves in the rabbit saphenous vein. J Pharmacol Exp Ther. 1999 Sep;290(3):1195-201. [10454495 ]
  5. Cohen Z, Bouchelet I, Olivier A, Villemure JG, Ball R, Stanimirovic DB, Hamel E: Multiple microvascular and astroglial 5-hydroxytryptamine receptor subtypes in human brain: molecular and pharmacologic characterization. J Cereb Blood Flow Metab. 1999 Aug;19(8):908-17. [10458598 ]
  6. Granas C, Larhammar D: Identification of an amino acid residue important for binding of methiothepin and sumatriptan to the human 5-HT(1B) receptor. Eur J Pharmacol. 1999 Sep 10;380(2-3):171-81. [10513577 ]
  7. Russell MG, Matassa VG, Pengilley RR, van Niel MB, Sohal B, Watt AP, Hitzel L, Beer MS, Stanton JA, Broughton HB, Castro JL: 3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists. J Med Chem. 1999 Dec 2;42(24):4981-5001. [10585208 ]
  8. Sternfeld F, Guiblin AR, Jelley RA, Matassa VG, Reeve AJ, Hunt PA, Beer MS, Heald A, Stanton JA, Sohal B, Watt AP, Street LJ: Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor. J Med Chem. 1999 Feb 25;42(4):677-90. [10052975 ]
  9. Chambers MS, Street LJ, Goodacre S, Hobbs SC, Hunt P, Jelley RA, Matassa VG, Reeve AJ, Sternfeld F, Beer MS, Stanton JA, Rathbone D, Watt AP, MacLeod AM: 3-(Piperazinylpropyl)indoles: selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1999 Feb 25;42(4):691-705. [10052976 ]
  10. Castro JL, Street LJ, Guiblin AR, Jelley RA, Russell MG, Sternfeld F, Beer MS, Stanton JA, Matassa VG: 3-[2-(Pyrrolidin-1-yl)ethyl]indoles and 3-[3-(piperidin-1-yl)propyl]indoles: agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B subtype. J Med Chem. 1997 Oct 24;40(22):3497-500. [9357514 ]
  11. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
  12. 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 ]
  13. Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
  14. Hamblin MW, Metcalf MA, McGuffin RW, Karpells S: Molecular cloning and functional characterization of a human 5-HT1B serotonin receptor: a homologue of the rat 5-HT1B receptor with 5-HT1D-like pharmacological specificity. Biochem Biophys Res Commun. 1992 Apr 30;184(2):752-9. [1315531 ]
  15. Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR: Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3630-4. [1565658 ]
  16. Glennon RA, Hong SS, Dukat M, Teitler M, Davis K: 5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist. J Med Chem. 1994 Sep 2;37(18):2828-30. [8071931 ]
  17. Ennis MD, Ghazal NB, Hoffman RL, Smith MW, Schlachter SK, Lawson CF, Im WB, Pregenzer JF, Svensson KA, Lewis RA, Hall ED, Sutter DM, Harris LT, McCall RB: Isochroman-6-carboxamides as highly selective 5-HT1D agonists: potential new treatment for migraine without cardiovascular side effects. J Med Chem. 1998 Jun 18;41(13):2180-3. [9632349 ]
  18. Egle I, MacLean N, Demchyshyn L, Edwards L, Slassi A, Tehim A: (R)-3-(N-methylpyrrolidin-2-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol e derivatives as high affinity h5-HT1B/1D ligands. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3419-21. [14505640 ]
  19. Egle I, MacLean N, Demchyshyn L, Edwards L, Slassi A, Tehim A: 3-(2-pyrrolidin-1-ylethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives as high affinity human 5-HT(1B/1D) ligands. Bioorg Med Chem Lett. 2004 Feb 9;14(3):727-9. [14741277 ]
  20. Choi SK, Green D, Ho A, Klein U, Marquess D, Taylor R, Turner SD: Designing selective, high affinity ligands of 5-HT1D receptor by covalent dimerization of 5-HT1F ligands derived from 4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide. J Med Chem. 2008 Jun 26;51(12):3609-16. doi: 10.1021/jm7011722. Epub 2008 May 29. [18507369 ]
  21. Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE: N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem. 1999 Feb 11;42(3):526-31. [9986723 ]
  22. Glennon RA, Hong SS, Bondarev M, Law H, Dukat M, Rakhi S, Power P, Fan E, Kinneau D, Kamboj R, Teitler M, Herrick-Davis K, Smith C: Binding of O-alkyl derivatives of serotonin at human 5-HT1D beta receptors. J Med Chem. 1996 Jan 5;39(1):314-22. [8568822 ]
  23. Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S: Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80. [9871581 ]
  24. Barf TA, de Boer P, Wikstrom H, Peroutka SJ, Swensson K, Ennis MD, Ghazal NB, McGuire JC, Smith MW: 5-HT1D receptor agonist properties of novel 2-[5-[[(trifluoromethyl)sulfonyl]oxy]indolyl]ethylamines and their use as synthetic intermediates. J Med Chem. 1996 Nov 22;39(24):4717-26. [8941384 ]
  25. Perez M, Fourrier C, Sigogneau I, Pauwels PJ, Palmier C, John GW, Valentin JP, Halazy S: Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors. J Med Chem. 1995 Sep 1;38(18):3602-7. [7658447 ]
  26. Halazy S, Perez M, Fourrier C, Pallard I, Pauwels PJ, Palmier C, John GW, Valentin JP, Bonnafous R, Martinez J: Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists. J Med Chem. 1996 Dec 6;39(25):4920-7. [8960551 ]
  27. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. Synapse. 2000 Feb;35(2):79-95. [10611634 ]
  28. Domenech T, Beleta J, Palacios JM: Characterization of human serotonin 1D and 1B receptors using [3H]-GR-125743, a novel radiolabelled serotonin 5HT1D/1B receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):328-34. [9303569 ]
  29. Meng CQ, Rakhit S, Lee DK, Kamboj R, McCallum KL, Mazzocco L, Dyne K, Slassi A: 5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: potential treatments for migraine. Bioorg Med Chem Lett. 2000 May 1;10(9):903-5. [10853656 ]
  30. Slassi A, Edwards L, O'Brien A, Meng CQ, Xin T, Seto C, Lee DK, MacLean N, Hynd D, Chen C, Wang H, Kamboj R, Rakhit S: 5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists. Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9. [10937729 ]
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
Inhibitory0.0012 uMNot AvailableBindingDB 50005835
Inhibitory0.0017 uMNot AvailableBindingDB 50005835
Inhibitory0.00199 uMNot AvailableBindingDB 50005835
Inhibitory0.002 uMNot AvailableBindingDB 50005835
Inhibitory0.00338 uMNot AvailableBindingDB 50005835
Inhibitory0.0034 uMNot AvailableBindingDB 50005835
Inhibitory0.0037 uMNot AvailableBindingDB 50005835
Inhibitory0.00371 uMNot AvailableBindingDB 50005835
Inhibitory0.0044 uMNot AvailableBindingDB 50005835
Inhibitory0.0055 uMNot AvailableBindingDB 50005835
Inhibitory0.0057 uMNot AvailableBindingDB 50005835
Inhibitory0.0077 uMNot AvailableBindingDB 50005835
Inhibitory0.0084 uMNot AvailableBindingDB 50005835
Inhibitory0.0085 uMNot AvailableBindingDB 50005835
Inhibitory0.0086 uMNot AvailableBindingDB 50005835
Inhibitory0.011 uMNot AvailableBindingDB 50005835
Inhibitory0.03 uMNot AvailableBindingDB 50005835
IC500.005 uMNot AvailableBindingDB 50005835
IC500.0067 uMNot AvailableBindingDB 50005835
IC500.0068 uMNot AvailableBindingDB 50005835
IC500.0073 uMNot AvailableBindingDB 50005835
IC500.03981 uMNot AvailableBindingDB 50005835
IC500.1 uMNot AvailableBindingDB 50005835
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Koran LM, Pallanti S, Quercioli L: Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2001 Apr;11(2):169-72. [11313163 ]
  3. Baxter LR Jr: Brain mediation of Anolis social dominance displays. III. Differential forebrain 3H-sumatriptan binding in dominant vs. submissive males. Brain Behav Evol. 2001 Apr;57(4):202-13. [11641558 ]
  4. Razzaque Z, Pickard JD, Ma QP, Shaw D, Morrison K, Wang T, Longmore J: 5-HT1B-receptors and vascular reactivity in human isolated blood vessels: assessment of the potential craniovascular selectivity of sumatriptan. Br J Clin Pharmacol. 2002 Mar;53(3):266-74. [11874390 ]
  5. Akin D, Gurdal H: Involvement of 5-HT1B and 5-HT1D receptors in sumatriptan mediated vasocontractile response in rabbit common carotid artery. Br J Pharmacol. 2002 May;136(2):177-82. [12010765 ]
  6. Zohar J, Kennedy JL, Hollander E, Koran LM: Serotonin-1D hypothesis of obsessive-compulsive disorder: an update. J Clin Psychiatry. 2004;65 Suppl 14:18-21. [15554784 ]
  7. Castro JL, Street LJ, Guiblin AR, Jelley RA, Russell MG, Sternfeld F, Beer MS, Stanton JA, Matassa VG: 3-[2-(Pyrrolidin-1-yl)ethyl]indoles and 3-[3-(piperidin-1-yl)propyl]indoles: agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B subtype. J Med Chem. 1997 Oct 24;40(22):3497-500. [9357514 ]
  8. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
  9. Sternfeld F, Guiblin AR, Jelley RA, Matassa VG, Reeve AJ, Hunt PA, Beer MS, Heald A, Stanton JA, Sohal B, Watt AP, Street LJ: Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor. J Med Chem. 1999 Feb 25;42(4):677-90. [10052975 ]
  10. Chambers MS, Street LJ, Goodacre S, Hobbs SC, Hunt P, Jelley RA, Matassa VG, Reeve AJ, Sternfeld F, Beer MS, Stanton JA, Rathbone D, Watt AP, MacLeod AM: 3-(Piperazinylpropyl)indoles: selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1999 Feb 25;42(4):691-705. [10052976 ]
  11. Russell MG, Matassa VG, Pengilley RR, van Niel MB, Sohal B, Watt AP, Hitzel L, Beer MS, Stanton JA, Broughton HB, Castro JL: 3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT(1D) receptor agonists. J Med Chem. 1999 Dec 2;42(24):4981-5001. [10585208 ]
  12. Street LJ, Baker R, Davey WB, Guiblin AR, Jelley RA, Reeve AJ, Routledge H, Sternfeld F, Watt AP, Beer MS, et al.: Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: potent agonists for 5-HT1D receptors. J Med Chem. 1995 May 12;38(10):1799-810. [7752204 ]
  13. 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 ]
  14. Choi SK, Green D, Ho A, Klein U, Marquess D, Taylor R, Turner SD: Designing selective, high affinity ligands of 5-HT1D receptor by covalent dimerization of 5-HT1F ligands derived from 4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide. J Med Chem. 2008 Jun 26;51(12):3609-16. doi: 10.1021/jm7011722. Epub 2008 May 29. [18507369 ]
  15. 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 ]
  16. Millan MJ, Newman-Tancredi A, Audinot V, Cussac D, Lejeune F, Nicolas JP, Coge F, Galizzi JP, Boutin JA, Rivet JM, Dekeyne A, Gobert A: Agonist and antagonist actions of yohimbine as compared to fluparoxan at alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and dopamine D(2) and D(3) receptors. Significance for the modulation of frontocortical monoaminergic transmission and depressive states. Synapse. 2000 Feb;35(2):79-95. [10611634 ]
  17. Ennis MD, Ghazal NB, Hoffman RL, Smith MW, Schlachter SK, Lawson CF, Im WB, Pregenzer JF, Svensson KA, Lewis RA, Hall ED, Sutter DM, Harris LT, McCall RB: Isochroman-6-carboxamides as highly selective 5-HT1D agonists: potential new treatment for migraine without cardiovascular side effects. J Med Chem. 1998 Jun 18;41(13):2180-3. [9632349 ]
  18. Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
  19. Egle I, MacLean N, Demchyshyn L, Edwards L, Slassi A, Tehim A: (R)-3-(N-methylpyrrolidin-2-ylmethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol e derivatives as high affinity h5-HT1B/1D ligands. Bioorg Med Chem Lett. 2003 Oct 20;13(20):3419-21. [14505640 ]
  20. Egle I, MacLean N, Demchyshyn L, Edwards L, Slassi A, Tehim A: 3-(2-pyrrolidin-1-ylethyl)-5-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives as high affinity human 5-HT(1B/1D) ligands. Bioorg Med Chem Lett. 2004 Feb 9;14(3):727-9. [14741277 ]
  21. Hamblin MW, Metcalf MA: Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8. [1652050 ]
  22. Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE: N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem. 1999 Feb 11;42(3):526-31. [9986723 ]
  23. Slassi A, Edwards L, O'Brien A, Meng CQ, Xin T, Seto C, Lee DK, MacLean N, Hynd D, Chen C, Wang H, Kamboj R, Rakhit S: 5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor agonists. Bioorg Med Chem Lett. 2000 Aug 7;10(15):1707-9. [10937729 ]
  24. Barf TA, de Boer P, Wikstrom H, Peroutka SJ, Swensson K, Ennis MD, Ghazal NB, McGuire JC, Smith MW: 5-HT1D receptor agonist properties of novel 2-[5-[[(trifluoromethyl)sulfonyl]oxy]indolyl]ethylamines and their use as synthetic intermediates. J Med Chem. 1996 Nov 22;39(24):4717-26. [8941384 ]
  25. Weinshank RL, Zgombick JM, Macchi MJ, Branchek TA, Hartig PR: Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3630-4. [1565658 ]
  26. Domenech T, Beleta J, Palacios JM: Characterization of human serotonin 1D and 1B receptors using [3H]-GR-125743, a novel radiolabelled serotonin 5HT1D/1B receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):328-34. [9303569 ]
  27. Perez M, Fourrier C, Sigogneau I, Pauwels PJ, Palmier C, John GW, Valentin JP, Halazy S: Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors. J Med Chem. 1995 Sep 1;38(18):3602-7. [7658447 ]
  28. Halazy S, Perez M, Fourrier C, Pallard I, Pauwels PJ, Palmier C, John GW, Valentin JP, Bonnafous R, Martinez J: Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists. J Med Chem. 1996 Dec 6;39(25):4920-7. [8960551 ]
  29. Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S: Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80. [9871581 ]
  30. Meng CQ, Rakhit S, Lee DK, Kamboj R, McCallum KL, Mazzocco L, Dyne K, Slassi A: 5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: potential treatments for migraine. Bioorg Med Chem Lett. 2000 May 1;10(9):903-5. [10853656 ]
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
Inhibitory0.23 uMNot AvailableBindingDB 50005835
Inhibitory0.255 uMNot AvailableBindingDB 50005835
Inhibitory0.25703 uMNot AvailableBindingDB 50005835
Inhibitory0.33 uMNot AvailableBindingDB 50005835
Inhibitory0.341 uMNot AvailableBindingDB 50005835
Inhibitory0.4071 uMNot AvailableBindingDB 50005835
Inhibitory0.44 uMNot AvailableBindingDB 50005835
Inhibitory1.02329 uMNot AvailableBindingDB 50005835
IC500.39811 uMNot AvailableBindingDB 50005835
IC500.50119 uMNot AvailableBindingDB 50005835
References
  1. Johnson DE, Rollema H, Schmidt AW, McHarg AD: Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain. Eur J Pharmacol. 2001 Aug 17;425(3):203-10. [11513839 ]
  2. Street LJ, Baker R, Davey WB, Guiblin AR, Jelley RA, Reeve AJ, Routledge H, Sternfeld F, Watt AP, Beer MS, et al.: Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: potent agonists for 5-HT1D receptors. J Med Chem. 1995 May 12;38(10):1799-810. [7752204 ]
  3. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  4. Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE: N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem. 1999 Feb 11;42(3):526-31. [9986723 ]
  5. Pauwels PJ, Van Gompel P, Leysen JE: Activity of serotonin (5-HT) receptor agonists, partial agonists and antagonists at cloned human 5-HT1A receptors that are negatively coupled to adenylate cyclase in permanently transfected HeLa cells. Biochem Pharmacol. 1993 Jan 26;45(2):375-83. [8382063 ]
  6. Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
  7. Glennon RA, Hong SS, Dukat M, Teitler M, Davis K: 5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist. J Med Chem. 1994 Sep 2;37(18):2828-30. [8071931 ]
  8. Glennon RA, Hong SS, Bondarev M, Law H, Dukat M, Rakhi S, Power P, Fan E, Kinneau D, Kamboj R, Teitler M, Herrick-Davis K, Smith C: Binding of O-alkyl derivatives of serotonin at human 5-HT1D beta receptors. J Med Chem. 1996 Jan 5;39(1):314-22. [8568822 ]
  9. Barf TA, de Boer P, Wikstrom H, Peroutka SJ, Swensson K, Ennis MD, Ghazal NB, McGuire JC, Smith MW: 5-HT1D receptor agonist properties of novel 2-[5-[[(trifluoromethyl)sulfonyl]oxy]indolyl]ethylamines and their use as synthetic intermediates. J Med Chem. 1996 Nov 22;39(24):4717-26. [8941384 ]
  10. Ennis MD, Ghazal NB, Hoffman RL, Smith MW, Schlachter SK, Lawson CF, Im WB, Pregenzer JF, Svensson KA, Lewis RA, Hall ED, Sutter DM, Harris LT, McCall RB: Isochroman-6-carboxamides as highly selective 5-HT1D agonists: potential new treatment for migraine without cardiovascular side effects. J Med Chem. 1998 Jun 18;41(13):2180-3. [9632349 ]
  11. Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S: Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80. [9871581 ]
  12. Perez M, Fourrier C, Sigogneau I, Pauwels PJ, Palmier C, John GW, Valentin JP, Halazy S: Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors. J Med Chem. 1995 Sep 1;38(18):3602-7. [7658447 ]
  13. Halazy S, Perez M, Fourrier C, Pallard I, Pauwels PJ, Palmier C, John GW, Valentin JP, Bonnafous R, Martinez J: Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists. J Med Chem. 1996 Dec 6;39(25):4920-7. [8960551 ]
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
Inhibitory0.0229 uMNot AvailableBindingDB 50005835
Inhibitory0.023 uMNot AvailableBindingDB 50005835
Inhibitory0.0257 uMNot AvailableBindingDB 50005835
IC500.027 uMNot AvailableBindingDB 50005835
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Razzaque Z, Heald MA, Pickard JD, Maskell L, Beer MS, Hill RG, Longmore J: Vasoconstriction in human isolated middle meningeal arteries: determining the contribution of 5-HT1B- and 5-HT1F-receptor activation. Br J Clin Pharmacol. 1999 Jan;47(1):75-82. [10073743 ]
  3. Pauwels PJ, John GW: Present and future of 5-HT receptor agonists as antimigraine drugs. Clin Neuropharmacol. 1999 May-Jun;22(3):123-36. [10367177 ]
  4. Roy A, Brand NJ, Yacoub MH: Expression of 5-hydroxytryptamine receptor subtype messenger RNA in interstitial cells from human heart valves. J Heart Valve Dis. 2000 Mar;9(2):256-60; discussion 260-1. [10772044 ]
  5. Cohen ML, Schenck K: Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5-HT(1F) receptor agonists and PGF(2alpha). Br J Pharmacol. 2000 Oct;131(3):562-8. [11015308 ]
  6. Janssen P, Tack J, Sifrim D, Meulemans AL, Lefebvre RA: Influence of 5-HT1 receptor agonists on feline stomach relaxation. Eur J Pharmacol. 2004 May 25;492(2-3):259-67. [15178373 ]
  7. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
  8. Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
  9. Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA: Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408-12. [8380639 ]
  10. Xu YC, Johnson KW, Phebus LA, Cohen M, Nelson DL, Schenck K, Walker CD, Fritz JE, Kaldor SW, LeTourneau ME, Murff RE, Zgombick JM, Calligaro DO, Audia JE, Schaus JM: N-[3-(2-Dimethylaminoethyl)-2-methyl-1H- indol-5-yl]-4-fluorobenzamide: a potent, selective, and orally active 5-HT(1F) receptor agonist potentially useful for migraine therapy. J Med Chem. 2001 Nov 22;44(24):4031-4. [11708905 ]
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
Inhibitory0.376 uMNot AvailableBindingDB 50005835
Inhibitory>1 uMNot AvailableBindingDB 50005835
Inhibitory>10 uMNot AvailableBindingDB 50005835
IC505.5 uMNot AvailableBindingDB 50005835
IC507.94328 uMNot AvailableBindingDB 50005835
References
  1. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
  2. Street LJ, Baker R, Davey WB, Guiblin AR, Jelley RA, Reeve AJ, Routledge H, Sternfeld F, Watt AP, Beer MS, et al.: Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: potent agonists for 5-HT1D receptors. J Med Chem. 1995 May 12;38(10):1799-810. [7752204 ]
  3. Ennis MD, Ghazal NB, Hoffman RL, Smith MW, Schlachter SK, Lawson CF, Im WB, Pregenzer JF, Svensson KA, Lewis RA, Hall ED, Sutter DM, Harris LT, McCall RB: Isochroman-6-carboxamides as highly selective 5-HT1D agonists: potential new treatment for migraine without cardiovascular side effects. J Med Chem. 1998 Jun 18;41(13):2180-3. [9632349 ]
  4. Glennon RA, Hong SS, Dukat M, Teitler M, Davis K: 5-(Nonyloxy)tryptamine: a novel high-affinity 5-HT1D beta serotonin receptor agonist. J Med Chem. 1994 Sep 2;37(18):2828-30. [8071931 ]
  5. Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):621-9. [9225287 ]
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
Inhibitory2.08929 uMNot AvailableBindingDB 50005835
Inhibitory2.34422 uMNot AvailableBindingDB 50005835
Inhibitory2.51188 uMNot AvailableBindingDB 50005835
Inhibitory2.52 uMNot AvailableBindingDB 50005835
IC502.4 uMNot AvailableBindingDB 50005835
References
  1. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
  2. Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
  3. Zgombick JM, Schechter LE, Macchi M, Hartig PR, Branchek TA, Weinshank RL: Human gene S31 encodes the pharmacologically defined serotonin 5-hydroxytryptamine1E receptor. Mol Pharmacol. 1992 Aug;42(2):180-5. [1513320 ]
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
Inhibitory>10 uMNot AvailableBindingDB 50005835
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL: Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences. J Pharmacol Exp Ther. 1996 Feb;276(2):720-7. [8632342 ]
  3. Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):621-9. [9225287 ]
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
Inhibitory>10 uMNot AvailableBindingDB 50005835
IC507.94328 uMNot AvailableBindingDB 50005835
IC50>1 uMNot AvailableBindingDB 50005835
IC50>10 uMNot AvailableBindingDB 50005835
References
  1. Street LJ, Baker R, Davey WB, Guiblin AR, Jelley RA, Reeve AJ, Routledge H, Sternfeld F, Watt AP, Beer MS, et al.: Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: potent agonists for 5-HT1D receptors. J Med Chem. 1995 May 12;38(10):1799-810. [7752204 ]
  2. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
  3. Bonhaus DW, Weinhardt KK, Taylor M, DeSouza A, McNeeley PM, Szczepanski K, Fontana DJ, Trinh J, Rocha CL, Dawson MW, Flippin LA, Eglen RM: RS-102221: a novel high affinity and selective, 5-HT2C receptor antagonist. Neuropharmacology. 1997 Apr-May;36(4-5):621-9. [9225287 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>10 uMNot AvailableBindingDB 50005835
References
  1. Street LJ, Baker R, Davey WB, Guiblin AR, Jelley RA, Reeve AJ, Routledge H, Sternfeld F, Watt AP, Beer MS, et al.: Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: potent agonists for 5-HT1D receptors. J Med Chem. 1995 May 12;38(10):1799-810. [7752204 ]
  2. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
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
Inhibitory2.6 uMNot AvailableBindingDB 50005835
Inhibitory>10 uMNot AvailableBindingDB 50005835
References
  1. 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 ]
  2. Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, Medhurst AD: Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modeling. Mol Pharmacol. 2003 Dec;64(6):1295-308. [14645659 ]
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
Inhibitory>0.218 uMNot AvailableBindingDB 50005835
References
  1. Barf TA, de Boer P, Wikstrom H, Peroutka SJ, Swensson K, Ennis MD, Ghazal NB, McGuire JC, Smith MW: 5-HT1D receptor agonist properties of novel 2-[5-[[(trifluoromethyl)sulfonyl]oxy]indolyl]ethylamines and their use as synthetic intermediates. J Med Chem. 1996 Nov 22;39(24):4717-26. [8941384 ]
  2. Ennis MD, Ghazal NB, Hoffman RL, Smith MW, Schlachter SK, Lawson CF, Im WB, Pregenzer JF, Svensson KA, Lewis RA, Hall ED, Sutter DM, Harris LT, McCall RB: Isochroman-6-carboxamides as highly selective 5-HT1D agonists: potential new treatment for migraine without cardiovascular side effects. J Med Chem. 1998 Jun 18;41(13):2180-3. [9632349 ]
General Function:
Serotonin receptor activity
Specific Function:
Not Available
Gene Name:
HTR1F
Uniprot ID:
Q9P2Q4
Molecular Weight:
41605.37 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.027 uMNot AvailableBindingDB 50005835
References
  1. MacLeod AM, Street LJ, Reeve AJ, Jelley RA, Sternfeld F, Beer MS, Stanton JA, Watt AP, Rathbone D, Matassa VG: Selective, orally active 5-HT1D receptor agonists as potential antimigraine agents. J Med Chem. 1997 Oct 24;40(22):3501-3. [9357515 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins.
Gene Name:
HTR5A
Uniprot ID:
P47898
Molecular Weight:
40254.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.501 uMNot AvailableBindingDB 50005835
References
  1. Castro JL, Baker R, Guiblin AR, Hobbs SC, Jenkins MR, Russell MG, Beer MS, Stanton JA, Scholey K, Hargreaves RJ, et al.: Synthesis and biological activity of 3-[2-(dimethylamino)ethyl]-5-[(1,1-dioxo-5-methyl-1,2,5-thiadiazolidin- 2-yl)-methyl]-1H-indole and analogues: agonists for the 5-HT1D receptor. J Med Chem. 1994 Sep 16;37(19):3023-32. [7932524 ]
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC506.7 uMNot AvailableBindingDB 50005835
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]