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
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
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18644039
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL224 |
8.4 null [pKi] | ||
Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15322733 |
9.1 nM [Ki] | ||
Target ID: CHEMBL225 |
8.6 null [pKi] | ||
Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8226867 |
83.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Preventing | SANSERT Approved UseFor 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 Date1962 |
Cmax
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 |
T1/2
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: |
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 |
Disc. AE: Vomiting, Cramps... AEs leading to discontinuation/dose reduction: Vomiting Sources: Cramps Peripheral vasoconstriction (severe) |
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: |
unhealthy |
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 |
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 |
PubMed
Title | Date | PubMed |
---|---|---|
Cardiac and pulmonary fibrosis during methysergide therapy for headache. | 1967 |
|
Retroperitoneal fibrosis secondary to methysergide bimaleate. | 1967 May 27 |
|
Comparative trial of serotonin antagonists in the management of migraine. | 1970 May 9 |
|
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 |
|
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 |
|
Indications for surgical replacement of the mitral valve. With particular reference to common and uncommon causes of mitral regurgitation. | 1979 Jul |
|
Effect of drugs influencing central serotonergic mechanisms on haloperidol-induced catalepsy. | 1979 Mar 29 |
|
The influence of cerebral 5-hydroxytryptamine on catalepsy induced by brain-amine depleting neuroleptics or by cholinomimetics. | 1979 Oct |
|
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 |
|
Antagonism of drug-induced yawning and penile erections in rats. | 1986 Mar 18 |
|
Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. | 1992 Apr 15 |
|
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 |
|
Neurotransmitter-mediated open-field behavioral action of CGRP. | 1999 |
|
Agonist high and low affinity state ratios predict drug intrinsic activity and a revised ternary complex mechanism at serotonin 5-HT(2A) and 5-HT(2C) receptors. | 2000 Feb |
|
Hyperalgesia induced by Asp49 and Lys49 phospholipases A2 from Bothrops asper snake venom: pharmacological mediation and molecular determinants. | 2003 May |
|
Methysergide-induced retroperitoneal fibrosis and pericardial effusion. | 2004 May |
|
Binding of tryptamine analogs at h5-HT1E receptors: a structure-affinity investigation. | 2004 May 15 |
|
Evidence for a spinal serotonergic control of the peripheral inflammation in the rat. | 2005 Apr 1 |
|
[3H]LY334370, a novel radioligand for the 5-HT1F receptor. I. In vitro characterization of binding properties. | 2005 Mar |
|
Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae). | 2009 Apr 21 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/sansert.html
Usual adult dose 4-8 mg daily. Tablets to be given with meals
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12770929
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)
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 17:19:23 GMT 2023
by
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Record UNII |
XZA9HY6Z98
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C47794
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LIVERTOX |
628
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WHO-VATC |
QN02CA04
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WHO-ATC |
N02CA04
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XZA9HY6Z98
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100000092396
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9681
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6911
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584020
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m7483
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206-644-0
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361-37-5
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C66123
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DB00247
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CHEMBL1065
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METHYSERGIDE
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DTXSID2023307
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1000
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