T3DB: Sumatriptan

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (14)XML

Targets (14)

Record Information

Version

2.0

Creation Date

2009-07-21 20:27:23 UTC

Update Date

2014-12-24 20:25:52 UTC

Accession Number

T3D2856

Identification

Common Name

Sumatriptan

Class

Small Molecule

Description

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. 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

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

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 Formula

C₁₄H₂₁N₃O₂S

Average Molecular Mass

295.400 g/mol

Monoisotopic Mass

295.135 g/mol

CAS Registry Number

103628-46-2

IUPAC Name

1-{3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}-N-methylmethanesulfonamide

Traditional Name

sumatriptan

SMILES

CNS(=O)(=O)CC1=CC2=C(NC=C2CCN(C)C)C=C1

InChI Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indoles and derivatives

Sub Class

Tryptamines and derivatives

Direct Parent

Tryptamines 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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

sulfonamide (CHEBI:10650 )
tryptamines (CHEBI:10650 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Brain

Pathways

Not Available

Applications

Biological Roles

serotonergic agonist

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	169-171°C
Boiling Point	Not Available
Solubility	21.4 mg/ml
LogP	0.93

Predicted Properties

Property	Value	Source
Water Solubility	0.13 g/L	ALOGPS
logP	1.17	ALOGPS
logP	0.74	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	11.24	ChemAxon
pKa (Strongest Basic)	9.54	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	65.2 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	82.08 m³·mol⁻¹	ChemAxon
Polarizability	32.31 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0zfr-7390000000-5809ad2270f77ffcec79	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-03di-0190000000-c12ee3ac5f29c3420996	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0a4i-2910000000-8769dc29dcac8fede7d1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0002-0390000000-cdddf05865e6d570c337	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0a4i-2910000000-8769dc29dcac8fede7d1	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-001i-1090000000-b0360ed354c3c7a76195	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0a4i-7970000000-4a9c99ffaf927876bb55	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000t-0090000000-42a6041e68fbb33f3c3c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0uxr-1290000000-18f63d6714d369042ced	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a59-1910000000-b311f02f2295ff294573	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-3090000000-23dacc0baf4eac1e818a	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00mo-9280000000-45a6f0dbb82744e4f102	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-01r6-9120000000-ca48d4e064a2f6323651	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03dl-9000000000-a75e9a0167fac95c8ca3	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03dl-9530000000-af10011e851a42315cd8	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4l-2900000000-e271d3cf647593f64e67	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0090000000-7a6d991d417845eb044c	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0zg4-2890000000-0b86cdf68f0a940df967	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9510000000-e92db5fc8036751fb26f	2021-09-22	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0a4i-9400000000-93cc7dc7e521f98aa292	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Subcutaneous, Oral, Nasal, Transdermal

Mechanism of Toxicity

The 5-HT_1B and 5-HT_1D 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.

Metabolism

Hepatic. 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of migraine attacks with or without aura.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Symptoms of overdose include convulsions, tremor, paralysis, inactivity, ptosis, erythema of the extremities, abnormal respiration, cyanosis, ataxia, mydriasis, salivation, and lacrimation.

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

10650

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Sumatriptan

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Sumatriptan

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.

MSDS

Link

General References

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 ]
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 ]
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 ]
Drugs.com [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Targets

Target Details

1. 5-hydroxytryptamine receptor 1B

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:: HTR1B
Uniprot ID:: P28222
Molecular Weight:: 43567.535 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0231 uM	Not Available	BindingDB 50005835
Inhibitory	0.024 uM	Not Available	BindingDB 50005835
Inhibitory	0.02511 uM	Not Available	BindingDB 50005835
Inhibitory	0.028 uM	Not Available	BindingDB 50005835
Inhibitory	0.036 uM	Not Available	BindingDB 50005835
Inhibitory	0.0479 uM	Not Available	BindingDB 50005835
Inhibitory	0.06 uM	Not Available	BindingDB 50005835
Inhibitory	0.06165 uM	Not Available	BindingDB 50005835
Inhibitory	0.0012 uM	Not Available	BindingDB 50005835
Inhibitory	0.00199 uM	Not Available	BindingDB 50005835
Inhibitory	0.002 uM	Not Available	BindingDB 50005835
Inhibitory	0.0034 uM	Not Available	BindingDB 50005835
Inhibitory	0.0055 uM	Not Available	BindingDB 50005835
Inhibitory	0.0064 uM	Not Available	BindingDB 50005835
Inhibitory	0.0077 uM	Not Available	BindingDB 50005835
Inhibitory	0.00776 uM	Not Available	BindingDB 50005835
Inhibitory	0.0091 uM	Not Available	BindingDB 50005835
Inhibitory	0.00933 uM	Not Available	BindingDB 50005835
Inhibitory	0.0096 uM	Not Available	BindingDB 50005835
Inhibitory	0.01 uM	Not Available	BindingDB 50005835
Inhibitory	0.01096 uM	Not Available	BindingDB 50005835
Inhibitory	0.0191 uM	Not Available	BindingDB 50005835
Inhibitory	0.022 uM	Not Available	BindingDB 50005835
Inhibitory	0.023 uM	Not Available	BindingDB 50005835
IC50	0.01 uM	Not Available	BindingDB 50005835
IC50	0.011 uM	Not Available	BindingDB 50005835
IC50	0.016 uM	Not Available	BindingDB 50005835

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

2. 5-hydroxytryptamine receptor 1D

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
Gene Name:: HTR1D
Uniprot ID:: P28221
Molecular Weight:: 41906.38 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0012 uM	Not Available	BindingDB 50005835
Inhibitory	0.0017 uM	Not Available	BindingDB 50005835
Inhibitory	0.00199 uM	Not Available	BindingDB 50005835
Inhibitory	0.002 uM	Not Available	BindingDB 50005835
Inhibitory	0.00338 uM	Not Available	BindingDB 50005835
Inhibitory	0.0034 uM	Not Available	BindingDB 50005835
Inhibitory	0.0037 uM	Not Available	BindingDB 50005835
Inhibitory	0.00371 uM	Not Available	BindingDB 50005835
Inhibitory	0.0044 uM	Not Available	BindingDB 50005835
Inhibitory	0.0055 uM	Not Available	BindingDB 50005835
Inhibitory	0.0057 uM	Not Available	BindingDB 50005835
Inhibitory	0.0077 uM	Not Available	BindingDB 50005835
Inhibitory	0.0084 uM	Not Available	BindingDB 50005835
Inhibitory	0.0085 uM	Not Available	BindingDB 50005835
Inhibitory	0.0086 uM	Not Available	BindingDB 50005835
Inhibitory	0.011 uM	Not Available	BindingDB 50005835
Inhibitory	0.03 uM	Not Available	BindingDB 50005835
IC50	0.005 uM	Not Available	BindingDB 50005835
IC50	0.0067 uM	Not Available	BindingDB 50005835
IC50	0.0068 uM	Not Available	BindingDB 50005835
IC50	0.0073 uM	Not Available	BindingDB 50005835
IC50	0.03981 uM	Not Available	BindingDB 50005835
IC50	0.1 uM	Not Available	BindingDB 50005835

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Koran LM, Pallanti S, Quercioli L: Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder. Eur Neuropsychopharmacol. 2001 Apr;11(2):169-72. [11313163 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

3. 5-hydroxytryptamine receptor 1A

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:: HTR1A
Uniprot ID:: P08908
Molecular Weight:: 46106.335 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.23 uM	Not Available	BindingDB 50005835
Inhibitory	0.255 uM	Not Available	BindingDB 50005835
Inhibitory	0.25703 uM	Not Available	BindingDB 50005835
Inhibitory	0.33 uM	Not Available	BindingDB 50005835
Inhibitory	0.341 uM	Not Available	BindingDB 50005835
Inhibitory	0.4071 uM	Not Available	BindingDB 50005835
Inhibitory	0.44 uM	Not Available	BindingDB 50005835
Inhibitory	1.02329 uM	Not Available	BindingDB 50005835
IC50	0.39811 uM	Not Available	BindingDB 50005835
IC50	0.50119 uM	Not Available	BindingDB 50005835

References

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 ]
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 ]
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 ]
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 ]
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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

4. 5-hydroxytryptamine receptor 1F

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:: HTR1F
Uniprot ID:: P30939
Molecular Weight:: 41708.505 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0229 uM	Not Available	BindingDB 50005835
Inhibitory	0.023 uM	Not Available	BindingDB 50005835
Inhibitory	0.0257 uM	Not Available	BindingDB 50005835
IC50	0.027 uM	Not Available	BindingDB 50005835

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
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 ]
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 ]

Target Details

5. 5-hydroxytryptamine receptor 2A

General Function:: Virus receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:: HTR2A
Uniprot ID:: P28223
Molecular Weight:: 52602.58 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.376 uM	Not Available	BindingDB 50005835
Inhibitory	>1 uM	Not Available	BindingDB 50005835
Inhibitory	>10 uM	Not Available	BindingDB 50005835
IC50	5.5 uM	Not Available	BindingDB 50005835
IC50	7.94328 uM	Not Available	BindingDB 50005835

References

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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

6. 5-hydroxytryptamine receptor 1E

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:: HTR1E
Uniprot ID:: P28566
Molecular Weight:: 41681.57 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	2.08929 uM	Not Available	BindingDB 50005835
Inhibitory	2.34422 uM	Not Available	BindingDB 50005835
Inhibitory	2.51188 uM	Not Available	BindingDB 50005835
Inhibitory	2.52 uM	Not Available	BindingDB 50005835
IC50	2.4 uM	Not Available	BindingDB 50005835

References

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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
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 ]

Target Details

7. 5-hydroxytryptamine receptor 2B

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:: HTR2B
Uniprot ID:: P41595
Molecular Weight:: 54297.41 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>10 uM	Not Available	BindingDB 50005835

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 ]
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 ]

Target Details

8. 5-hydroxytryptamine receptor 2C

General Function:: Serotonin receptor activity
Specific Function:: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:: HTR2C
Uniprot ID:: P28335
Molecular Weight:: 51820.705 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>10 uM	Not Available	BindingDB 50005835
IC50	7.94328 uM	Not Available	BindingDB 50005835
IC50	>1 uM	Not Available	BindingDB 50005835
IC50	>10 uM	Not Available	BindingDB 50005835

References

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 ]
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 ]
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 ]

Target Details

9. 5-hydroxytryptamine receptor 3A

General Function:: Voltage-gated potassium channel activity
Specific Function:: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
Gene Name:: HTR3A
Uniprot ID:: P46098
Molecular Weight:: 55279.835 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	>10 uM	Not Available	BindingDB 50005835

References

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 ]
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 ]

Target Details

10. 5-hydroxytryptamine receptor 6

General Function:: Serotonin receptor activity
Specific Function:: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:: HTR6
Uniprot ID:: P50406
Molecular Weight:: 46953.625 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	2.6 uM	Not Available	BindingDB 50005835
Inhibitory	>10 uM	Not Available	BindingDB 50005835

References

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 ]
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 ]

Target Details

11. D(2) dopamine receptor

General Function:: Potassium channel regulator activity
Specific Function:: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:: DRD2
Uniprot ID:: P14416
Molecular Weight:: 50618.91 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>0.218 uM	Not Available	BindingDB 50005835

References

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 ]
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 ]

Target Details

12. 5-hydroxytryptamine (Serotonin) receptor 1F

General Function:: Serotonin receptor activity
Specific Function:: Not Available
Gene Name:: HTR1F
Uniprot ID:: Q9P2Q4
Molecular Weight:: 41605.37 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.027 uM	Not Available	BindingDB 50005835

References

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 ]

Target Details

13. 5-hydroxytryptamine receptor 5A

General Function:: Serotonin receptor activity
Specific Function:: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins.
Gene Name:: HTR5A
Uniprot ID:: P47898
Molecular Weight:: 40254.69 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.501 uM	Not Available	BindingDB 50005835

References

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 ]

Target Details

14. Multidrug and toxin extrusion protein 1

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

Type	Value	Assay Type	Assay Source
IC50	6.7 uM	Not Available	BindingDB 50005835

References

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 ]

Sumatriptan (T3D2856)

Structure for T3D2856: Sumatriptan

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