METHYSERGIDE DIMALEATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H27N3O2.2C4H4O4
Molecular Weight	585.6023
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.CC[C@@H](CO)NC(=O)[C@H]1CN(C)[C@@H]2CC3=CN(C)C4=C3C(=CC=C4)C2=C1

InChI

InChIKey=FUYUWMZGKBNTIB-VMTAUMJGSA-N

InChI=1S/C21H27N3O2.2C4H4O4/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;2*5-3(6)1-2-4(7)8/h5-8,10,14-15,19,25H,4,9,11-12H2,1-3H3,(H,22,26);2*1-2H,(H,5,6)(H,7,8)/b;2*2-1-/t14-,15+,19-;;/m1../s1

HIDE SMILES / InChI

Molecular Formula	C21H27N3O2
Molecular Weight	353.458
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://www.migraines.org/treatment/tsmthysr.htm | https://www.drugs.com/pro/sansert.html | https://www.migrainetrust.org/living-with-migraine/treatments/methysergide/ | https://www.ncbi.nlm.nih.gov/pubmed/9793694

Methysergide is an oral, synthetic ergot alkaloid, structurally related to the oxytocic agent methylergonovine and to the potent hallucinogen LSD. Methysergide is used prophylactically to reduce the frequency and intensity of severe vascular headaches. Although methysergide is an ergot alkaloid, it is a weak vasoconstrictor and oxytocic. Methysergide is a more potent antagonist of peripheral serotonin receptors than other ergot alkaloids. Methysergide is not just a 5HT2 antagonist, it is also a 5HT1 agonist. Although methysergide and sumatriptan both stimulate serotonin receptors centrally, methysergide is intended for prophylaxis while sumatriptan is indicated for treatment of an acute attack. Methysergide was approved by the FDA in 1962. Methysergide was formerly used for prophylaxis of cluster headaches/migraine headaches, but is no longer recommended due to retroperitoneal/retropulmonary fibrosis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9793694 \| https://www.ncbi.nlm.nih.gov/pubmed/17067154	Antagonist 2849	8.4 null [pKi]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15322733	Antagonist 2849	9.1 nM [Ki]
Serotonin 2c (5-HT2c) receptor 131 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17067154 \| https://www.ncbi.nlm.nih.gov/pubmed/15322733	Antagonist 2849	8.6 null [pKi]
Serotonin 7 (5-HT7) receptor 30 Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8226867	Antagonist 2849	83.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Vascular headaches 3 Sources: http://www.migraines.org/treatment/tsmthysr.htm https://www.migrainetrust.org/living-with-migraine/treatments/methysergide/	Preventing		Approved 8583	SANSERT Approved Use For the prevention or reduction of intensity and frequency of vascular headaches in the following kinds of patients: Patients suffering from one or more severe vascular headaches per week. Patients suffering from vascular headaches that are uncontrollable or so severe that preventive therapy is indicated regardless of the frequency of the attack. Launch Date 1962

C_max

Value	Dose	Co-administered	Analyte	Population
5 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
33 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	0.753 mg single, intravenous dose: 0.753 mg route of administration: Intravenous experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
563.9 nM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2027 nM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	0.753 mg single, intravenous dose: 0.753 mg route of administration: Intravenous experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
62 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
45 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	0.753 mg single, intravenous dose: 0.753 mg route of administration: Intravenous experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
15 mg 1 times / day multiple, oral Studied dose Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6061274	unhealthy, 17 - 24 years Health Status: unhealthy Age Group: 17 - 24 years Sources: https://pubmed.ncbi.nlm.nih.gov/6061274	Sources: https://pubmed.ncbi.nlm.nih.gov/6061274
10 \|5 mg 1 times / day multiple\|multiple, oral\|intravenous Dose: 10 \|5 mg, 1 times / day Route: oral\|intravenous Route: multiple\|multiple Dose: 10 \|5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6061274	unhealthy, 17 - 24 years Health Status: unhealthy Age Group: 17 - 24 years Sources: https://pubmed.ncbi.nlm.nih.gov/6061274	Sources: https://pubmed.ncbi.nlm.nih.gov/6061274
10 \|5\| 2 mg 1 times / day multiple\|multiple\|single, oral\|intravenous\|intrathecal Dose: 10 \|5\| 2 mg, 1 times / day Route: oral\|intravenous\|intrathecal Route: multiple\|multiple\|single Dose: 10 \|5\| 2 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6061274	unhealthy, 17 - 24 years Health Status: unhealthy Age Group: 17 - 24 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/6061274	Sources: https://pubmed.ncbi.nlm.nih.gov/6061274
0.753 mg 1 times / day single, intravenous Dose: 0.753 mg, 1 times / day Route: intravenous Route: single Dose: 0.753 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3709634	healthy, 23-28 years Health Status: healthy Age Group: 23-28 years Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/3709634	Sources: https://pubmed.ncbi.nlm.nih.gov/3709634
8 mg 1 times / day multiple, oral Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14171102	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/14171102	Disc. AE: Vomiting, Cramps... AEs leading to discontinuation/dose reduction: Vomiting Cramps Peripheral vasoconstriction (severe) Sources: https://pubmed.ncbi.nlm.nih.gov/14171102

AEs

AE	Significance	Dose	Population
Cramps	Disc. AE	8 mg 1 times / day multiple, oral Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14171102	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/14171102
Vomiting	Disc. AE	8 mg 1 times / day multiple, oral Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14171102	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/14171102
Peripheral vasoconstriction	severe Disc. AE	8 mg 1 times / day multiple, oral Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/14171102	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/14171102

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BSEP 554	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw2MDIwIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDQ4NTI1MyJ9fQ%3D%3D	yes [IC50 33.07 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://go.drugbank.com/drugs/DB00247, https://link.springer.com/chapter/10.1007/978-1-4614-7495-1_67	yes

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01CCZ3
ABI Chem	AC1L1TKV
AK Scientific	G831
ApexBio Technology	B5046
BOC Sciences	129-49-7
BOC Sciences	361-37-5
ChemFish Tokyo co.,ltd	9681	http://www.chemfish.co.jp/index.php?id=3958&project=product
Chemieliva Pharmaceutical Co., Ltd	PBCM1287632
Chemspace	CSSB00102657330	https://chem-space.com/CSSB00102657330
Compound Cloud	5281073
Compound Cloud	9681
eMolecules	110007777
eMolecules	195184164
eMolecules	206903759
eMolecules	300416771
MolPort	MolPort-003-958-638
MuseChem	I007878	https://www.musechem.com/product/I007878.html
NovoSeek	9681
Sigma Aldrich	1440003
Sigma Aldrich	1440003\|USP
Sigma Aldrich	M137
Sigma Aldrich	M137\|SIGMA
Tetrahedron	TS82759
THE BioTek	bt-364989	https://www.thebiotek.com/product/others/bt-364989
Tocris	1064
Toronto Research Chemicals	M329350
Toronto Research Chemicals	M329359
ZINC	ZINC000053151228	http://zinc15.docking.org/substances/ZINC000053151228

PubMed

Title	Date	PubMed
Abdominal angina as a complication of methysergide maleate therapy.	1967 Jan 9	6071145
Silent retroperitoneal fibrosis associated with methysergide therapy.	1968 Oct 28	5695652
Cardiac murmurs and endocardial fibrosis associated with methysergide therapy.	1974 Nov	4420941
Methysergide in the treatment of narcolepsy.	1975 Apr	164849
Skeletal muscle necrosis following membrane-active drugs plus serotonin.	1976 May	6632
Methysergide-induced heart disease: a case of multivalvular and myocardial fibrosis.	1977 Nov	912852
Migraine and systemic scleroderma.	1978 Apr	646367
[Methysergide-induced fibrosis. Directives for preventive treatment of migraine with methysergide].	1979 Jan 29	760308
The influence of 5-HT receptor blocking agents on the behavioral effects of analgesics in rats.	1980	6771831
Methysergide induced mitral valvular insufficiency.	1980 Jan	7353368
[Distal mesenteric arteritis: a rare complication of D. methylsergide treatment (author's transl)].	1981 Apr	6790701
[Reversible distal mesenteric arteritis after continuous prolonged treatment with methylsergide].	1981 Mar 21	7220274
Arterial complications of migraine treatment with methysergide and parenteral ergotamine.	1982 Jul 24	6807440
[Sclerodermiform syndrome caused by methysergide].	1984 Apr 7	6727469
Simulation of acute myopericarditis by constrictive pericardial disease with endomyocardial fibrosis due to methysergide therapy.	1984 Jul	6736450
Chronic pain after methysergide: a new cause of ischemic monomelic neuropathy.	1991 Nov-Dec	1663389
Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype.	1992 Jun 15	1608964
Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.	1993 Apr 15	7682702
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.	1993 Dec	7508328
Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs.	1993 Mar	7680751
Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys.	1993 Oct	8106150
A useful method for differential evaluation of anti-inflammatory effects due to cyclooxygenase and 5-lipoxygenase inhibitions in mice.	1994 Aug	7990266
Cloning and characterisation of the human 5-HT5A serotonin receptor.	1994 Dec 5	7988681
Serotonin syndrome complicating migraine pharmacotherapy.	1996 Aug	8869767
Alniditan, a new 5-hydroxytryptamine1D agonist and migraine-abortive agent: ligand-binding properties of human 5-hydroxytryptamine1D alpha, human 5-hydroxytryptamine1D beta, and calf 5-hydroxytryptamine1D receptors investigated with [3H]5-hydroxytryptamine and [3H]alniditan.	1996 Dec	8967979
Two amino acid differences in the sixth transmembrane domain are partially responsible for the pharmacological differences between the 5-HT1D beta and 5-HT1E 5-hydroxytryptamine receptors.	1996 Nov	8863519
Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells.	1997 Apr-May	9225298
Mast cell involvement in the rat paw oedema response to 1,8-cineole, the main constituent of eucalyptus and rosemary oils.	1997 Jul 23	9274987
Involvement of 5-hydroxytryptamine and bradykinin in the hyperalgesia induced in rats by collagenase from Clostridium histolyticum.	1997 May	9151293
Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b).	1997 Sep	9298538
Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand binding site of the 5-hydroxytryptamine6 receptor.	1997 Sep	9284367
Activating mutations of the serotonin 5-HT2C receptor.	1997 Sep	9282936
Effects of EGIS-7625, a selective and competitive 5-HT2B receptor antagonist.	2003 Sep-Nov	15107597
Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors.	2004 Aug	15322733
Binding of tryptamine analogs at h5-HT1E receptors: a structure-affinity investigation.	2004 May 15	15110837
[Neuromediatorial mechanisms of analgesia during general anesthesia].	2004 May-Jun	15314848
Methysergide-induced scleroderma-like changes of the legs.	2005 Jul	16029366
[3H]LY334370, a novel radioligand for the 5-HT1F receptor. I. In vitro characterization of binding properties.	2005 Mar	15900510
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.	2006 Mar 27	16545797
Drug-induced fibrotic valvular heart disease.	2009 Aug 15	19683643

Patents

Sample Use Guides

In Vivo Use Guide

Usual adult dose 4-8 mg daily. Tablets to be given with meals

Route of Administration: Oral

In Vitro Use Guide

The actions of 5-HT were significantly reversed by the 5-HT(1/2/5/7) receptor antagonist methysergide (0.5 uM)

Substance Class	Chemical Created by `admin` on `Mon Mar 31 21:08:11 GMT 2025` Edited by `admin` on `Mon Mar 31 21:08:11 GMT 2025`
Record UNII	EMS84N8S7Y
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHYSERGIDE DIMALEATE

Common Name

English

ERGOLINE-8-CARBOXAMIDE, 9,10-DIDEHYDRO-N-(1-(HYDROXYMETHYL)PROPYL)-1,6-DIMETHYL-, (8.BETA.(S))-, (2Z)-2-BUTENEDIOATE (1:2) (SALT)

Preferred Name

English

ERGOLINE-8-CARBOXAMIDE, 9,10-DIDEHYDRO-N-(1-(HYDROXYMETHYL)PROPYL)-1,6-DIMETHYL-, (8.BETA.(S))-, (Z)-2-BUTENEDIOATE (1:2) (SALT)

Systematic Name

English

Code System Code Type Description

CAS

120220-03-3

Created by admin on Mon Mar 31 21:08:11 GMT 2025 , Edited by admin on Mon Mar 31 21:08:11 GMT 2025

PRIMARY

PUBCHEM

21158509

Created by admin on Mon Mar 31 21:08:11 GMT 2025 , Edited by admin on Mon Mar 31 21:08:11 GMT 2025

PRIMARY

FDA UNII

EMS84N8S7Y

Created by admin on Mon Mar 31 21:08:11 GMT 2025 , Edited by admin on Mon Mar 31 21:08:11 GMT 2025

PRIMARY

Related Record Type Details


					XZA9HY6Z98

METHYSERGIDE

PARENT -> SALT/SOLVATE

Related Record Type Details


					XZA9HY6Z98

METHYSERGIDE

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: http://www.migraines.org/treatment/tsmthysr.htm | https://www.drugs.com/pro/sansert.html | https://www.migrainetrust.org/living-with-migraine/treatments/methysergide/ | https://www.ncbi.nlm.nih.gov/pubmed/9793694

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Cmax

AUC

T1/2

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://www.migraines.org/treatment/tsmthysr.htm | https://www.drugs.com/pro/sansert.html | https://www.migrainetrust.org/living-with-migraine/treatments/methysergide/ | https://www.ncbi.nlm.nih.gov/pubmed/9793694

C_max

T_1/2

Drug as perpetrator