METHYSERGIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H27N3O2
Molecular Weight	353.458
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC3=CN(C)C4=C3C(=CC=C4)C1=C[C@H](CN2C)C(=O)N[C@@H](CC)CO

InChI

InChIKey=KPJZHOPZRAFDTN-ZRGWGRIASA-N

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

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

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 230 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9793694 \| https://www.ncbi.nlm.nih.gov/pubmed/17067154	Antagonist 2760	8.4 null [pKi]
Serotonin 2b (5-HT2b) receptor 60 Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15322733	Antagonist 2760	9.1 nM [Ki]
Serotonin 2c (5-HT2c) receptor 122 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17067154 \| https://www.ncbi.nlm.nih.gov/pubmed/15322733	Antagonist 2760	8.6 null [pKi]
Serotonin 7 (5-HT7) receptor 31 Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8226867	Antagonist 2760	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 8360	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 -2.48832E11

C_max

Value	Dose	Co-administered	Analyte	Population
33 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
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

AUC

Value	Dose	Co-administered	Analyte	Population
2027 nM × min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
45 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3709634/	1 mg single, intravenous dose: 1 mg route of administration: Intravenous experiment type: SINGLE co-administered:		METHYSERGIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
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

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 n = 14 Health Status: unhealthy Condition: schizophrenia Age Group: 17 - 24 years Population Size: 14 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 (complex) 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 n = 12 Health Status: unhealthy Condition: schizophrenia Age Group: 17 - 24 years Population Size: 12 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 (complex) 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 n = 6 Health Status: unhealthy Condition: schizophrenia Age Group: 17 - 24 years Sex: M+F Population Size: 6 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 n = 5 Health Status: healthy Age Group: 23-28 years Sex: M Population Size: 5 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 1709

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 401

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BSEP 402	inhibitor 3240 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 1709	substrate 3326 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
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
THE BioTek	bt-364989	https://www.thebiotek.com/product/others/bt-364989
Tetrahedron	TS82759
Tocris	1064
Toronto Research Chemicals	M329350
Toronto Research Chemicals	M329359
ZINC	ZINC000053151228	http://zinc15.docking.org/substances/ZINC000053151228
eMolecules	110007777
eMolecules	195184164
eMolecules	206903759
eMolecules	300416771

PubMed

Title	Date	PubMed
Aortic obstruction associated with methysergide maleate therapy for headaches.	1966 Nov 21	5953401
Reversible mesenteric artery stenoses due to methysergide maleate.	1966 Oct 31	5953309
Cardiac and pulmonary fibrosis during methysergide therapy for headache.	1967	6028242
Vascular adventitial fibrosis in a patient taking methysergide maleate.	1968 Mar 18	5694374
Silent retroperitoneal fibrosis associated with methysergide therapy.	1968 Oct 28	5695652
Methysergide in mania.	1969 Feb 22	4179254
Complications of methysergide therapy: retroperitoneal fibrosis, mitral regurgitation, edema, and hemolytic anemia.	1970 Jul 13	5467905
Psychiatric adverse reactions to methysergide.	1972 Apr	5024073
Skeletal muscle necrosis following membrane-active drugs plus serotonin.	1976 May	6632
Methysergide therapy causing vascular insufficiency of the upper limb.	1977 Mar	844003
Methysergide-induced heart disease: a case of multivalvular and myocardial fibrosis.	1977 Nov	912852
Migraine and systemic scleroderma.	1978 Apr	646367
Methysergide therapy and constrictive pericarditis.	1978 Feb	626452
[Methysergide-induced fibrosis. Directives for preventive treatment of migraine with methysergide].	1979 Jan 29	760308
Indications for surgical replacement of the mitral valve. With particular reference to common and uncommon causes of mitral regurgitation.	1979 Jul	377933
The influence of cerebral 5-hydroxytryptamine on catalepsy induced by brain-amine depleting neuroleptics or by cholinomimetics.	1979 Oct	40649
The influence of 5-HT receptor blocking agents on the behavioral effects of analgesics in rats.	1980	6771831
[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
p,p'-DDT-induced myoclonus in mice: the effect of enhanced 5-HT neurotransmission.	1985 Feb	2986413
Antagonism of drug-induced yawning and penile erections in rats.	1986 Mar 18	2872065
Methysergide-induced lower extremity arterial insufficiency.	1986 Sep	2944904
St. Anthony's fire, then and now: a case report and historical review.	1987 Jul	3300918
[Isolated stenosis of the popliteal artery after treatment with methysergide. An anatomopathologic study].	1990	2212880
Chronic pain after methysergide: a new cause of ischemic monomelic neuropathy.	1991 Nov-Dec	1663389
Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.	1993 Apr 15	7682702
Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype.	1993 Aug 25	8394362
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.	1993 Dec	7508328
Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.	1993 Jan 15	8380639
Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization.	1993 Mar	8450829
Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes.	1993 Mar 15	8384716
Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.	1993 Nov 5	8226867
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
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
Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.	1996 Jan	8522988
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
Methysergide-induced valvular heart disease: a report of 2 cases.	2006	17099974
Potential vascular alpha1-adrenoceptor blocking properties of an array of 5-HT receptor ligands in the rat.	2006 Mar 27	16545797
Drugs and valvular heart disease.	2007 Jan 4	17202450
Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae).	2009 Apr 21	19429325
Drug-induced fibrotic valvular heart disease.	2009 Aug 15	19683643
5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.	2009 Jul 31	19649285

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 `Thu Jul 06 22:43:02 UTC 2023` Edited by `admin` on `Thu Jul 06 22:43:02 UTC 2023`
Record UNII	XZA9HY6Z98
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHYSERGIDE

Official Name

English

METHYSERGIDE [MI]

Common Name

English

METHYSERGIDE [HSDB]

Common Name

English

METHYSERGIDE [VANDF]

Common Name

English

methysergide [INN]

Common Name

English

(8β)-9,10-Didehydro-N-[(1S)-1-(hydroxymethyl)propyl]-1,6-dimethylergoline-8-carboxamide

Systematic Name

English

METHYSERGIDE [USAN]

Common Name

English

METHYSERGIDE [MART.]

Common Name

English

Methysergide [WHO-DD]

Common Name

English

ERGOMETRINE MALEATE IMPURITY G [EP IMPURITY]

Common Name

English

(8β)-N-[(2S)-1-hydroxybutan-2-yl]-1,6-dimethyl-9,10-didehydroergoline-8-carboxamide

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47794