T3DB: Methysergide

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (11)XML

Targets (11)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:23 UTC

Update Date

2014-12-24 20:25:50 UTC

Accession Number

T3D2726

Identification

Common Name

Methysergide

Class

Small Molecule

Description

An ergot derivative that is a congener of lysergic acid diethylamide. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.

Compound Type

Amide
Amine
Drug
Metabolite
Organic Compound
Serotonin Antagonist
Sympatholytic
Synthetic Compound
Vasoconstrictor Agent

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(+)-9,10-Didehydro-N-(1-(hydroxymethyl)propyl)-1,6-dimethylergoline-8beta-carboxamide
(+)-N-(1-(Hydroxymethyl)propyl)-1-methyl-D-lysergamide
1-Methyl-D-lysergic acid butanolamide
1-Methyl-dextro-lysergic acid (+)-1-hydroxy-2-butylamide
1-Methyllysergic acid butanolamide
1-Methylmethylergonovine
9,10-Didehydro-N-(1-(hydroxymethyl)propyl)-1,6-dimethylergoline-8-carboxamide
Deseril
Desernil
Methyllysergic acid butanolamide
Methysergid
Methysergidum
Metisergida
Metisergide
Metisergido
N-(1-(Hydroxymethyl)propyl)-1-methyl-dextro-(+)-lysergamide
N-(alpha-(Hydroxymethyl)propyl)-1-methyl-dextro-lysergamide
Sansert

Chemical Formula

C₂₁H₂₇N₃O₂

Average Molecular Mass

353.458 g/mol

Monoisotopic Mass

353.210 g/mol

CAS Registry Number

361-37-5

IUPAC Name

(4R,7R)-N-(1-hydroxybutan-2-yl)-6,11-dimethyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(15),2,9,12(16),13-pentaene-4-carboxamide

Traditional Name

methysergide

SMILES

[H]C(CC)(CO)N=C(O)[C@@]1([H])CN(C)[C@]2([H])CC3=CN(C)C4=CC=CC(=C34)C2=C1

InChI Identifier

InChI=1S/C21H27N3O2/c1-4-15(12-25)22-21(26)14-8-17-16-6-5-7-18-20(16)13(10-23(18)2)9-19(17)24(3)11-14/h5-8,10,14-15,19,25H,4,9,11-12H2,1-3H3,(H,22,26)/t14-,15?,19-/m1/s1

InChI Key

InChIKey=KPJZHOPZRAFDTN-NQUBZZJWSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.

Kingdom

Organic compounds

Super Class

Alkaloids and derivatives

Class

Ergoline and derivatives

Sub Class

Lysergic acids and derivatives

Direct Parent

Lysergamides

Alternative Parents

Substituents

Lysergic acid amide
Indoloquinoline
Benzoquinoline
Pyrroloquinoline
Quinoline-3-carboxamide
N-alkylindole
Quinoline
3-alkylindole
Indole
Indole or derivatives
Isoindole or derivatives
Aralkylamine
Benzenoid
N-methylpyrrole
Substituted pyrrole
Heteroaromatic compound
Pyrrole
Tertiary aliphatic amine
Carboxamide group
Amino acid or derivatives
Tertiary amine
Secondary carboxylic acid amide
Organoheterocyclic compound
Carboxylic acid derivative
Azacycle
Organonitrogen compound
Organopnictogen compound
Organic oxygen compound
Amine
Alcohol
Carbonyl group
Organooxygen compound
Primary alcohol
Organic nitrogen compound
Organic oxide
Hydrocarbon derivative
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

monocarboxylic acid amide (CHEBI:584020 )
ergot alkaloid (CHEBI:584020 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	195°C
Boiling Point	Not Available
Solubility	2.24e-01 g/L
LogP	1.5

Predicted Properties

Property	Value	Source
Water Solubility	0.22 g/L	ALOGPS
logP	2.22	ALOGPS
logP	1.82	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	15.01	ChemAxon
pKa (Strongest Basic)	7.85	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	57.5 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	104.47 m³·mol⁻¹	ChemAxon
Polarizability	40.41 Å³	ChemAxon
Number of Rings	4	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	splash10-03di-4495000000-d0cc0e065ac2a249f139	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-03di-3390100000-c2e2183c67e221dc8c1d	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udr-1009000000-633c43ec26d6039658e4	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00kr-5095000000-47b5108f6a3ebd949236	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0c0c-3390000000-7d1562a443e084f1ea99	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0009000000-9ba72bc3d8d89f6a4388	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0ff9-2059000000-819b11151769bcbb6445	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-05g3-6090000000-5d7ac6f788f61ce26929	2016-08-04	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0019000000-5a70e47475b13679f8e3	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0udr-0059000000-d42a975e818a2288348e	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-000i-0090000000-22d20459936ae0d0b518	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0009000000-c66b7fea4f08e0ca5b51	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0udi-1019000000-b7eebee23bde51802f58	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0kfx-6193000000-c592c6e25521a17d4740	2021-09-22	View Spectrum

Toxicity Profile

Route of Exposure

Ingestion (4), rapid.

Mechanism of Toxicity

Ergoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. Methysergide as a serotonin antagonists acts on central nervous system, which directly stimulates the smooth muscle leading to vasoconstriction. Some alpha-adrenergic blocking activity has also been reported. Suggestions have been made by investigators as to the mechanism whereby Methysergide produces its clinical effects, but this has not been finally established, although it may be related to the antiserotonin effect. (1, 3, 4, 5)

Metabolism

Methysergide is metabolized in the liver. (1)

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

Methysergide is a synthetic derivative of the ergoline family, which occur naturally in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi like other ergoline alkaloids. Methysergide antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. It is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome and is sold under the brand names Sansert and Deseril in 2mg dosages. (8, 11)

Minimum Risk Level

Not Available

Health Effects

Ingestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (2)

Symptoms

Few cases of acute methysergide intoxication have been reported. The possible symptom complex is therefore not fully known. The following symptoms are based on these few case reports. Euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness have been reported in a child with a dose of 20-24 mg of methysergide. In adults, peripheral vasospasm, with diminished or absent pulses, coldness, mottling and cyanosis, has been observed at a dose of 200 mg. Ischemic tissue damage has not been reported in acute overdosage with methysergide.

Treatment

Treatment for overdose consists of removal of the offending drug by induction of emesis, or gastric lavage in the case of very recent intake, repeat dose administration of activated charcoal and catharsis. I.V. fluids may be given as a general supportive measure. Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. (7)

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

584020

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Methysergide

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Methysergide

References

Synthesis Reference

Not Available

MSDS

T3D2726.pdf

General References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Richard JL: Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. Epub 2007 Jul 31. [17719115 ]
Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. [10418123 ]
Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
Kvernmo T, Hartter S, Burger E: A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. [16982285 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]
Wikipedia. Ergoline. Last Updated 2 April 2010. [Link]
Wikipedia. Ergotism. Last Updated 6 April 2010. [Link]
Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. [Link]
Wikipedia. Methysergide. Last Updated 17 February 2010. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 5-hydroxytryptamine receptor 2A

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.00158 uM	Not Available	BindingDB 50031942
Inhibitory	0.00245 uM	Not Available	BindingDB 50031942
Inhibitory	0.00331 uM	Not Available	BindingDB 50031942
Inhibitory	0.00398 uM	Not Available	BindingDB 50031942
Inhibitory	0.01 uM	Not Available	BindingDB 50031942

References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Castilho VM, Avanzi V, Brandao ML: Antinociception elicited by aversive stimulation of the inferior colliculus. Pharmacol Biochem Behav. 1999 Mar;62(3):425-31. [10080233 ]
Geerts IS, Matthys KE, Herman AG, Bult H: Involvement of 5-HT1B receptors in collar-induced hypersensitivity to 5-hydroxytryptamine of the rabbit carotid artery. Br J Pharmacol. 1999 Jul;127(6):1327-36. [10455282 ]
Shaw AM, Brown C, Irvine J, Bunton DC, MacDonald A: Role of the 5-HT(2A)receptor and alpha(1)-adrenoceptor in the contractile response of rat pulmonary artery to 5-HT in the presence and absence of nitric oxide. Pulm Pharmacol Ther. 2000;13(6):277-85. [11061982 ]
Prins NH, Akkermans LM, Lefebvre RA, Schuurkes JA: Characterization of the receptors involved in the 5-HT-induced excitation of canine antral longitudinal muscle. Br J Pharmacol. 2001 Nov;134(6):1351-9. [11704657 ]
Connor JD, Rasheed H, Gilani AH, Cheema M, Rizvi Z, Saeed SA: Second messengers in platelet aggregation evoked by serotonin and A23187, a calcium ionophore. Life Sci. 2001 Oct 26;69(23):2759-64. [11720080 ]
Furlotti G, Alisi MA, Apicella C, Capezzone de Joannon A, Cazzolla N, Costi R, Cuzzucoli Crucitti G, Garrone B, Iacovo A, Magaro G, Mangano G, Miele G, Ombrato R, Pescatori L, Polenzani L, Rosi F, Vitiello M, Di Santo R: Discovery and pharmacological profile of new 1H-indazole-3-carboxamide and 2H-pyrrolo[3,4-c]quinoline derivatives as selective serotonin 4 receptor ligands. J Med Chem. 2012 Nov 26;55(22):9446-66. doi: 10.1021/jm300573d. Epub 2012 Oct 24. [23043420 ]
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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]
Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM: The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol. 1995 Jun;115(4):622-8. [7582481 ]
Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, Bickerdike M: Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23. Epub 2004 Jul 30. [15322733 ]
Hedner E, Sjogren M, Frandberg PA, Johansson T, Goransson U, Dahlstrom M, Jonsson P, Nyberg F, Bohlin L: Brominated cyclodipeptides from the marine sponge Geodia barretti as selective 5-HT ligands. J Nat Prod. 2006 Oct;69(10):1421-4. [17067154 ]

Target Details

2. 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	0.00036 uM	Not Available	BindingDB 50031942
Inhibitory	0.00064 uM	Not Available	BindingDB 50031942
Inhibitory	0.00151 uM	Not Available	BindingDB 50031942
Inhibitory	0.00159 uM	Not Available	BindingDB 50031942
Inhibitory	0.00165 uM	Not Available	BindingDB 50031942
Inhibitory	0.00794 uM	Not Available	BindingDB 50031942
Inhibitory	0.0091 uM	Not Available	BindingDB 50031942
Inhibitory	0.15 uM	Not Available	BindingDB 50031942

References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, Bickerdike M: Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23. Epub 2004 Jul 30. [15322733 ]
Wainscott DB, Sasso DA, Kursar JD, Baez M, Lucaites VL, Nelson DL: [3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2b (5-HT2B) receptor. Naunyn Schmiedebergs Arch Pharmacol. 1998 Jan;357(1):17-24. [9459568 ]
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 ]
Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM: The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol. 1995 Jun;115(4):622-8. [7582481 ]
Glusa E, Pertz HH: Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors. Br J Pharmacol. 2000 Jun;130(3):692-8. [10821800 ]
Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL: Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41. [11104741 ]
Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL: 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro. Mol Pharmacol. 2003 Jun;63(6):1223-9. [12761331 ]

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	0.01698 uM	Not Available	BindingDB 50031942

References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Scrogin KE, Johnson AK, Brooks VL: Methysergide delays the decompensatory responses to severe hemorrhage by activating 5-HT(1A) receptors. Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1776-86. [11049861 ]
Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. [14501155 ]
Sugimoto Y, Inoue K, Yamada J: Involvement of 5-HT(2) receptor in imipramine-induced hyperglycemia in mice. Horm Metab Res. 2003 Sep;35(9):511-6. [14517765 ]
Skyba DA, Radhakrishnan R, Rohlwing JJ, Wright A, Sluka KA: Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord. Pain. 2003 Nov;106(1-2):159-68. [14581123 ]
Pranzatelli MR, Balletti J: Characterization of 5-hydroxytryptamine 1A-like binding sites in human ganglioneuroblastoma. Neurosci Lett. 1991 Oct 28;132(1):117-20. [1838579 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]

Target Details

4. 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	0.00095 uM	Not Available	BindingDB 50031942
Inhibitory	0.00158 uM	Not Available	BindingDB 50031942
Inhibitory	0.0025 uM	Not Available	BindingDB 50031942
Inhibitory	0.00447 uM	Not Available	BindingDB 50031942

References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 ]
Bonhaus DW, Bach C, DeSouza A, Salazar FH, Matsuoka BD, Zuppan P, Chan HW, Eglen RM: The pharmacology and distribution of human 5-hydroxytryptamine2B (5-HT2B) receptor gene products: comparison with 5-HT2A and 5-HT2C receptors. Br J Pharmacol. 1995 Jun;115(4):622-8. [7582481 ]
Hedner E, Sjogren M, Frandberg PA, Johansson T, Goransson U, Dahlstrom M, Jonsson P, Nyberg F, Bohlin L: Brominated cyclodipeptides from the marine sponge Geodia barretti as selective 5-HT ligands. J Nat Prod. 2006 Oct;69(10):1421-4. [17067154 ]
Knight AR, Misra A, Quirk K, Benwell K, Revell D, Kennett G, Bickerdike M: Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23. Epub 2004 Jul 30. [15322733 ]

Target Details

5. 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	0.059 uM	Not Available	BindingDB 50031942
Inhibitory	0.21877 uM	Not Available	BindingDB 50031942
Inhibitory	0.228 uM	Not Available	BindingDB 50031942
Inhibitory	0.22908 uM	Not Available	BindingDB 50031942
Inhibitory	0.32359 uM	Not Available	BindingDB 50031942

References

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 ]
Leonhardt S, Herrick-Davis K, Titeler M: Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. J Neurochem. 1989 Aug;53(2):465-71. [2664084 ]
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

6. 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	0.0036 uM	Not Available	BindingDB 50031942
Inhibitory	0.00758 uM	Not Available	BindingDB 50031942
Inhibitory	0.02511 uM	Not Available	BindingDB 50031942
Inhibitory	0.16218 uM	Not Available	BindingDB 50031942

References

Matsumoto I, Combs MR, Jones DJ: Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]-5-hydroxytryptamine release. J Pharmacol Exp Ther. 1992 Feb;260(2):614-26. [1738111 ]
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 ]
Boess FG, Martin IL: Molecular biology of 5-HT receptors. Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317. [7984267 ]

Target Details

7. 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	0.00363 uM	Not Available	BindingDB 50031942
Inhibitory	0.025 uM	Not Available	BindingDB 50031942

References

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

Target Details

8. 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	0.03388 uM	Not Available	BindingDB 50031942
Inhibitory	0.034 uM	Not Available	BindingDB 50031942

References

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

Target Details

9. 5-hydroxytryptamine receptor 6

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

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.18 uM	Not Available	BindingDB 50031942
Inhibitory	0.372 uM	Not Available	BindingDB 50031942

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 ]
Bard JA, Zgombick J, Adham N, Vaysse P, Branchek TA, Weinshank RL: Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase. J Biol Chem. 1993 Nov 5;268(31):23422-6. [8226867 ]

Target Details

10. 5-hydroxytryptamine receptor 7

General Function:: Serotonin receptor activity
Specific Function:: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:: HTR7
Uniprot ID:: P34969
Molecular Weight:: 53554.43 Da

References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. [14501155 ]

Target Details

11. Sigma non-opioid intracellular receptor 1

General Function:: Opioid receptor activity
Specific Function:: Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:: SIGMAR1
Uniprot ID:: Q99720
Molecular Weight:: 25127.52 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.912 uM	Not Available	BindingDB 50031942

References

Myers AM, Charifson PS, Owens CE, Kula NS, McPhail AT, Baldessarini RJ, Booth RG, Wyrick SD: Conformational analysis, pharmacophore identification, and comparative molecular field analysis of ligands for the neuromodulatory sigma 3 receptor. J Med Chem. 1994 Nov 25;37(24):4109-17. [7990111 ]

Methysergide (T3D2726)

Structure for T3D2726: Methysergide

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

References

Binding/Activity Constants

References