U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H27N3O2
Molecular Weight 353.4588
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHYSERGIDE

SMILES

CC[C@@]([H])(CO)N=C([C@]1([H])C=C2c3cccc4c3c(C[C@@]2([H])N(C)C1)cn4C)O

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
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.

Originator

Curator's Comment:: Methysergide was introduced in the clinic in 1959 as a highly specific 5-HT antagonist in the preventive treatment of migraine by the Italian neurologist Federigo Sicuteri

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
33 nM
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
2027 nM × min
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
45 min
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
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

Doses

DosePopulationAdverse 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:
unhealthy, 17 - 24 years
n = 14
Health Status: unhealthy
Condition: schizophrenia
Age Group: 17 - 24 years
Population Size: 14
Sources:
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:
unhealthy, 17 - 24 years
n = 12
Health Status: unhealthy
Condition: schizophrenia
Age Group: 17 - 24 years
Population Size: 12
Sources:
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:
unhealthy, 17 - 24 years
n = 6
Health Status: unhealthy
Condition: schizophrenia
Age Group: 17 - 24 years
Sex: M+F
Population Size: 6
Sources:
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:
healthy, 23-28 years
n = 5
Health Status: healthy
Age Group: 23-28 years
Sex: M
Population Size: 5
Sources:
8 mg 1 times / day multiple, oral
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Disc. AE: Vomiting, Cramps...
AEs leading to
discontinuation/dose reduction:
Vomiting
Cramps
Peripheral vasoconstriction (severe)
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
unhealthy
Health Status: unhealthy
Sources:
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:
unhealthy
Health Status: unhealthy
Sources:
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:
unhealthy
Health Status: unhealthy
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Aortic obstruction associated with methysergide maleate therapy for headaches.
1966 Nov 21
Reversible mesenteric artery stenoses due to methysergide maleate.
1966 Oct 31
Cardiac and pulmonary fibrosis during methysergide therapy for headache.
1967
Abdominal angina as a complication of methysergide maleate therapy.
1967 Jan 9
Vascular adventitial fibrosis in a patient taking methysergide maleate.
1968 Mar 18
Silent retroperitoneal fibrosis associated with methysergide therapy.
1968 Oct 28
Mitral regurgitation occurring during methsergide (Sansert) therapy.
1969 Nov 1
Complications of methysergide therapy: retroperitoneal fibrosis, mitral regurgitation, edema, and hemolytic anemia.
1970 Jul 13
Comparative trial of serotonin antagonists in the management of migraine.
1970 May 9
[Methysergide-induced retroperitoneal fibrosis].
1972
Psychiatric adverse reactions to methysergide.
1972 Apr
[Treatment of hyperemesis with the antiserotonin substance, UML-491 (deseril)].
1973 Jun 8
Development of heart valve lesions during methysergide therapy.
1974 May 18
Cardiac murmurs and endocardial fibrosis associated with methysergide therapy.
1974 Nov
Skeletal muscle necrosis following membrane-active drugs plus serotonin.
1976 May
Methysergide therapy causing vascular insufficiency of the upper limb.
1977 Mar
Methysergide-induced heart disease: a case of multivalvular and myocardial fibrosis.
1977 Nov
Migraine and systemic scleroderma.
1978 Apr
Methysergide therapy and constrictive pericarditis.
1978 Feb
Lower extremity arterial insufficiency after long-term methysergide maleate therapy. Its evaluation with Doppler ultrasonic velocity detector.
1979 Aug
[Methysergide-induced fibrosis. Directives for preventive treatment of migraine with methysergide].
1979 Jan 29
The influence of 5-HT receptor blocking agents on the behavioral effects of analgesics in rats.
1980
Methysergide induced mitral valvular insufficiency.
1980 Jan
[Distal mesenteric arteritis: a rare complication of D. methylsergide treatment (author's transl)].
1981 Apr
[Reversible distal mesenteric arteritis after continuous prolonged treatment with methylsergide].
1981 Mar 21
Arterial complications of migraine treatment with methysergide and parenteral ergotamine.
1982 Jul 24
Two members of a distinct subfamily of 5-hydroxytryptamine receptors differentially expressed in rat brain.
1993 Apr 15
Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase.
1993 Aug
Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype.
1993 Aug 25
Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.
1993 Dec
Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase.
1993 Jan 15
Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor.
1993 Mar
Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization.
1993 Mar
Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs.
1993 Mar
Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes.
1993 Mar 15
Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.
1993 Nov 5
Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys.
1993 Oct
A useful method for differential evaluation of anti-inflammatory effects due to cyclooxygenase and 5-lipoxygenase inhibitions in mice.
1994 Aug
Cloning and characterisation of the human 5-HT5A serotonin receptor.
1994 Dec 5
Expression of functional mouse 5-HT5A serotonin receptor in the methylotrophic yeast Pichia pastoris: pharmacological characterization and localization.
1995 Dec 27
Serotonin syndrome complicating migraine pharmacotherapy.
1996 Aug
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
Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.
1996 Jan
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
Functional and radioligand binding characterization of rat 5-HT6 receptors stably expressed in HEK293 cells.
1997 Apr-May
Mast cell involvement in the rat paw oedema response to 1,8-cineole, the main constituent of eucalyptus and rosemary oils.
1997 Jul 23
Involvement of 5-hydroxytryptamine and bradykinin in the hyperalgesia induced in rats by collagenase from Clostridium histolyticum.
1997 May
Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7b).
1997 Sep
Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand binding site of the 5-hydroxytryptamine6 receptor.
1997 Sep
Activating mutations of the serotonin 5-HT2C receptor.
1997 Sep
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
Curator's Comment:: Constriction measurements and intracellular microelectrode recordings were performed in vitro on lymphatic vessels isolated from the guinea-pig mesentery to investigate whether 5-hydroxytryptamine (5-HT) affected lymphatic pumping and smooth muscle membrane potential. 5-HT decreased in a concentration-dependent manner the frequency of constrictions induced by intraluminal vessel perfusion. In nonperfused vessels, 5-HT hyperpolarized the lymphatic smooth muscle membrane potential and decreased the frequency and amplitude of spontaneous transient depolarizations (STDs).
The actions of 5-HT were significantly reversed by the 5-HT(1/2/5/7) receptor antagonist methysergide (0.5 uM)
Name Type Language
METHYSERGIDE
HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
METHYSERGIDE [MI]
Common Name English
METHYSERGIDE [HSDB]
Common Name English
METHYSERGIDE [WHO-DD]
Common Name English
METHYSERGIDE [VANDF]
Common Name English
METHYSERGIDE [INN]
Common Name English
METHYSERGIDE [USAN]
Common Name English
METHYSERGIDE [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47794
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
LIVERTOX 628
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
WHO-VATC QN02CA04
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
WHO-ATC N02CA04
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
Code System Code Type Description
FDA UNII
XZA9HY6Z98
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
PUBCHEM
9681
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
RXCUI
6911
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M7483
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
206-644-0
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
CAS
361-37-5
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
NCI_THESAURUS
C66123
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
EVMPD
SUB08880MIG
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
DRUG BANK
DB00247
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL1065
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
WIKIPEDIA
METHYSERGIDE
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
DRUG CENTRAL
1775
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY
INN
1000
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PRIMARY
MESH
D008784
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PRIMARY
IUPHAR
134
Created by admin on Sat Jun 26 09:31:07 UTC 2021 , Edited by admin on Sat Jun 26 09:31:07 UTC 2021
PRIMARY