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

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H25N3O2
Molecular Weight 339.4314
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHYLERGONOVINE

SMILES

[H][C@@]12CC3=CNC4=C3C(=CC=C4)C1=C[C@H](CN2C)C(=O)N[C@@H](CC)CO

InChI

InChIKey=UNBRKDKAWYKMIV-QWQRMKEZSA-N
InChI=1S/C20H25N3O2/c1-3-14(11-24)22-20(25)13-7-16-15-5-4-6-17-19(15)12(9-21-17)8-18(16)23(2)10-13/h4-7,9,13-14,18,21,24H,3,8,10-11H2,1-2H3,(H,22,25)/t13-,14+,18-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/006035Orig1S078.pdf

Methylergometrine (other names include methylergonovine, methylergobasin, methergine, and D-lysergic acid 1-butanolamide) is a synthetic analogue of ergonovine, a psychedelic alkaloid found in ergot, and many species of morning glory. In general, the effects of all the ergot alkaloids appear to results from their actions as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic receptors. The spectrum of effects depends on the agent, dosage, species, tissue, and experimental or physiological conditions. All of the alkaloids of ergot significantly increase the motor activity of the uterus. After small doses contractions are increased in force or frequency, or both, but are followed by a normal degree of relaxation. As the dose is increased, contractions become more forceful and prolonged, resting tonus is markedly increased, and sustained contracture can result. Methylergometrine acts directly on the smooth muscle of the uterus and increases the tone, rate, and amplitude of rhythmic contractions through binding and the resultant antagonism of the dopamine D1 receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss. Methylergometrine is used for the prevention and control of excessive bleeding following vaginal childbirth.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
METHERGINE

Approved Use

Following delivery of the placenta, for routine management of uterine atony, hemorrhage and subinvolution of the uterus. For control of uterine hemorrhage in the second stage of labor following delivery of the anterior shoulder.

Launch Date

1946
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5918 pg/mL
0.2 mg single, intramuscular
dose: 0.2 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
METHYLERGONOVINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
13889 pg × h/mL
0.2 mg single, intramuscular
dose: 0.2 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
METHYLERGONOVINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.39 h
0.2 mg single, intramuscular
dose: 0.2 mg
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
METHYLERGONOVINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
0.2 mg single, intramuscular
Overdose
Dose: 0.2 mg
Route: intramuscular
Route: single
Dose: 0.2 mg
Sources:
healthy, newborns
Health Status: healthy
Age Group: newborns
Sources:
Other AEs: Respiratory depression, Hypothermia...
Other AEs:
Respiratory depression
Hypothermia
Hypertonicity
Jerky movement NOS
Convulsions
Sources:
0.8 mg multiple, oral
Highest studied dose
healthy
Health Status: healthy
Condition: uterine atony and hemorrhage prophylaxis
Sex: F
Sources:
0.2 mg single, intravenous
Recommended
Dose: 0.2 mg
Route: intravenous
Route: single
Dose: 0.2 mg
Sources:
unhealthy
Health Status: unhealthy
Condition: uterine hemorrhage
Sources:
Other AEs: Hypertension, Cerebrovascular accident...
Other AEs:
Hypertension
Cerebrovascular accident
Sources:
AEs

AEs

AESignificanceDosePopulation
Convulsions
0.2 mg single, intramuscular
Overdose
Dose: 0.2 mg
Route: intramuscular
Route: single
Dose: 0.2 mg
Sources:
healthy, newborns
Health Status: healthy
Age Group: newborns
Sources:
Hypertonicity
0.2 mg single, intramuscular
Overdose
Dose: 0.2 mg
Route: intramuscular
Route: single
Dose: 0.2 mg
Sources:
healthy, newborns
Health Status: healthy
Age Group: newborns
Sources:
Hypothermia
0.2 mg single, intramuscular
Overdose
Dose: 0.2 mg
Route: intramuscular
Route: single
Dose: 0.2 mg
Sources:
healthy, newborns
Health Status: healthy
Age Group: newborns
Sources:
Jerky movement NOS
0.2 mg single, intramuscular
Overdose
Dose: 0.2 mg
Route: intramuscular
Route: single
Dose: 0.2 mg
Sources:
healthy, newborns
Health Status: healthy
Age Group: newborns
Sources:
Respiratory depression
0.2 mg single, intramuscular
Overdose
Dose: 0.2 mg
Route: intramuscular
Route: single
Dose: 0.2 mg
Sources:
healthy, newborns
Health Status: healthy
Age Group: newborns
Sources:
Cerebrovascular accident
0.2 mg single, intravenous
Recommended
Dose: 0.2 mg
Route: intravenous
Route: single
Dose: 0.2 mg
Sources:
unhealthy
Health Status: unhealthy
Condition: uterine hemorrhage
Sources:
Hypertension
0.2 mg single, intravenous
Recommended
Dose: 0.2 mg
Route: intravenous
Route: single
Dose: 0.2 mg
Sources:
unhealthy
Health Status: unhealthy
Condition: uterine hemorrhage
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina.
1991 Apr
Coronary artery spasm triggered by oral administration of methylergometrine.
1991 Aug 3
Misoprostol versus methylergometrine: pharmacokinetics in human milk.
2004 Dec
A comparison of propofol and ketamine as induction agents for cesarean section.
2004 Jul
Sublingual misoprostol versus methylergometrine for active management of the third stage of labor.
2004 Oct
[Tako-tsubo: a rare form of transient left ventricular dysfunction].
2005 Apr
Methylergonovine maleate (methergine) relieves postdural puncture headache in obstetric patients.
2005 Jan
Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist.
2005 May-Jun
Oral misoprostol versus injectable methylergometrine in management of the third stage of labor.
2005 Nov
Myocardial infarction and mortality caused by methylergonovine.
2005 Oct
The role of serendipity in drug discovery.
2006
Prevention of postpartum hemorrhage by uterotonic agents: comparison of oxytocin and methylergometrine in the management of the third stage of labor.
2006
Effect of enhancement of uterine involution and earlier initiation of post-partum cyclicity on the reproductive performance of buffalo.
2006
Is methergine alone sufficient in relieving postdural puncture headache?
2006
[Intraoperative anaphylactic shock induced by methylergometrine and oxytocin].
2006 Apr
Stability of oral liquid preparations of methylergometrine.
2006 Aug
[Heart and freezer: about one case of hypereosinophilia and coronary spasm].
2006 Aug
Improved migraine management in primary care: results of a patient treatment experience study using zolmitriptan orally disintegrating tablet.
2006 Dec
[B lynch suture for post partum heamorrhage due to uterine atony].
2006 Feb
Effect of estradiol 17beta upon coronary artery vasoconstrictor response to methylergometrine maleate in female menopausal patients.
2006 Feb 15
[Effects of methylergometrine and oxytocin on blood loss and uterine contraction during cesarean section].
2006 May
Oral misoprostol for the prevention of primary post-partum hemorrhage during third stage of labor.
2007 Dec
[Two cases of congenital airway obstruction managed with ex utero intrapartum treatment procedures: anesthetic implications].
2007 Jan
Prospective study of intramuscular ergometrine compared with intramuscular oxytocin for prevention of postpartum hemorrhage.
2007 Jun
Early lactation performance in primiparous and multiparous women in relation to different maternity home practices. A randomised trial in St. Petersburg.
2007 May 8
[Case report of a successful pregnancy following thrombolysis for acute myocardial infarction].
2007 Nov
Intraumbilical injection of uterotonics for retained placenta.
2007 Nov
A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active management of third stage of labour.
2007 Sep
Diagnosis and treatment of peripartum bleeding.
2008
Eclipsed mitral regurgitation: a new form of functional mitral regurgitation for an unusual cause of heart failure with normal ejection fraction.
2008
Complete uterine inversion during caesarean section: A case report.
2008 Aug 27
Prophylaxis of migraine: general principles and patient acceptance.
2008 Dec
[Case of peripartum cardiomyopathy developed after an emergency cesarean section--a case report].
2008 Feb
Efficacy of rectal misoprostol as second-line therapy for the treatment of primary postpartum hemorrhage.
2008 Mar
Signs of myocardial ischaemia after injection of oxytocin: a randomized double-blind comparison of oxytocin and methylergometrine during Caesarean section.
2008 May
History of methysergide in migraine.
2008 Nov
Bromocriptine, a dopamine D(2) receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC12 cells.
2008 Nov 19
Low-dose sublingual misoprostol versus methylergometrine for active management of the third stage of labor.
2008 Oct
Postpartum severe sinus bradycardia following methylergonovine administration.
2008 Sep-Oct
Early postpartum hemorrhage after induction of labor.
2008 Sep-Oct
Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics.
2009 Jul
Appetite suppressants, cardiac valve disease and combination pharmacotherapy.
2009 Jul-Aug
Management of cardiac arrest caused by coronary artery spasm: epinephrine/adrenaline versus nitrates.
2009 May-Jun
Efavirenz: a decade of clinical experience in the treatment of HIV.
2009 Nov
Emergent management of postpartum hemorrhage for the general and acute care surgeon.
2009 Nov 25
Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study.
2009 Nov 8
Association of ornithine transcarbamylase gene polymorphisms with hypertension and coronary artery vasomotion.
2009 Sep
Severe vaginal bleeding secondary to cesarean scar dehiscence following incomplete abortion management.
2010 Feb
Care during the third stage of labour: obstetricians views and practice in an Albanian maternity hospital.
2010 Jan 26
Human immunodeficiency virus and pregnancy.
2010 May
Patents

Sample Use Guides

Intramuscularly 1 mL, 0.2 mg, after delivery of the anterior shoulder, after delivery of the placenta, or during the puerperium. May be repeated as required, at intervals of 2-4 hours. Intravenously 1 mL, 0.2 mg, administered slowly over a period of no less than 60 seconds Orally One tablet, 0.2 mg, 3 or 4 times daily in the puerperium for a maximum of 1 week.
Route of Administration: Other
In Vitro Use Guide
Unknown
Name Type Language
METHYLERGONOVINE
MI   VANDF  
Common Name English
METHYLERGOMETRINE [HSDB]
Common Name English
(8.BETA.)-N-((1S)-1-(HYDROXYMETHYL)PROPYL)-6-METHYL-9,10-DIDEHYDROERGOLINE-8-CARBOXAMIDE
Systematic Name English
ERGOTYL
Brand Name English
(8β)-N-[(2S)-1-hydroxybutan-2-yl]-6-methyl-9,10-didehydroergoline-8-carboxamide
Systematic Name English
methylergometrine [INN]
Common Name English
ERGOMETRINE MALEATE IMPURITY D [EP IMPURITY]
Common Name English
METHYLERGONOVINE [VANDF]
Common Name English
Methylergometrine [WHO-DD]
Common Name English
METHYLERGONOVINE [MI]
Common Name English
METHYLERGOMETRINE
HSDB   INN   WHO-DD  
INN  
Official Name English
Classification Tree Code System Code
NCI_THESAURUS C47795
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NDF-RT N0000007618
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NDF-RT N0000175827
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WHO-VATC QG02AB01
Created by admin on Sat Dec 16 17:45:12 GMT 2023 , Edited by admin on Sat Dec 16 17:45:12 GMT 2023
WHO-ATC G02AC01
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WHO-VATC QG02AC01
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WHO-ATC G02AB01
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NDF-RT N0000007618
Created by admin on Sat Dec 16 17:45:12 GMT 2023 , Edited by admin on Sat Dec 16 17:45:12 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID00904978
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PRIMARY
MERCK INDEX
m7412
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PRIMARY Merck Index
NCI_THESAURUS
C74105
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PRIMARY
DAILYMED
W53L6FE61V
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PRIMARY
EVMPD
SUB08868MIG
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PRIMARY
INN
2900
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PRIMARY
RXCUI
6883
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PRIMARY RxNorm
PUBCHEM
8226
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PRIMARY
SMS_ID
100000080906
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PRIMARY
DRUG CENTRAL
1764
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PRIMARY
DRUG BANK
DB00353
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PRIMARY
CAS
113-42-8
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PRIMARY
HSDB
3364
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PRIMARY
LACTMED
Methylergonovine
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PRIMARY
ChEMBL
CHEMBL1201356
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PRIMARY
IUPHAR
150
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PRIMARY
FDA UNII
W53L6FE61V
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PRIMARY
MESH
D008755
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PRIMARY
ECHA (EC/EINECS)
204-027-0
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PRIMARY
WIKIPEDIA
METHYLERGOMETRINE
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PRIMARY