Identification

Name
Methylergometrine
Accession Number
DB00353  (APRD00739)
Type
Small Molecule
Groups
Approved
Description

A homolog of ergonovine containing one more CH2 group. (Merck Index, 11th ed)

Structure
Thumb
Synonyms
  • 9,10-Didehydro-N-[1-(hydroxymethyl)-propyl]-D-lysergamide
  • D-lysergic acid 1-butanolamide
  • Ergotyl
  • Methylergobasin
  • Methylergometrin
  • Méthylergométrine
  • Methylergometrine
  • Methylergometrinum
  • Methylergonovine
  • Metilergometrina
Product Ingredients
IngredientUNIICASInChI Key
Methylergometrine maleateIR84JPZ1RK57432-61-8NOFOWWRHEPHDCY-DAUURJMHSA-N
Methylergonovine tartrate5EDH242U9O6209-37-6KUTMUWFMKWZQBW-UQJJQXDBSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MethergineTablet, coated0.2 mg/1OralNovartis1946-11-192013-04-01Us0078 005420180907 15195 1fd9mbi
MethergineTablet, coated0.2 mg/1OralApotheca, Inc.2006-12-27Not applicableUs
MethergineTablet, coated0.2 mg/1Oralbryant ranch prepack1946-11-19Not applicableUs63629 379120180907 15195 flsol
MethergineTablet, coated0.2 mg/1OralPhysicians Total Care, Inc.1946-11-192007-06-30Us
MethergineTablet, coated0.2 mg/1OralPd Rx Pharmaceuticals, Inc.1946-11-192016-04-13Us00078 0054 05 nlmimage10 e208f107
MethergineInjection, solution0.2 mg/1mLIntramuscular; IntravenousNovartis2002-01-282015-03-01Us
MethergineTablet, coated0.2 mg/1OralDispensing Solutions, Inc.1946-11-19Not applicableUs
MethergineTablet, coated0.2 mg/1OralPd Rx Pharmaceuticals, Inc.1946-11-192016-04-13Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MethergineTablet0.2 mg/1OralAvera McKennan Hospital2016-06-232018-06-15Us
MethergineTablet0.2 mg/1OralLupin Pharma2016-04-04Not applicableUs
Methylergonovine MaleateInjection0.2 mg/1mLIntramuscular; IntravenousAkorn2011-03-02Not applicableUs
Methylergonovine MaleateInjection, solution0.2 mg/1mLIntramuscular; IntravenousAMERICAN REGENT, INC.2010-06-21Not applicableUs
Methylergonovine MaleateTablet0.2 mg/1OralWest-Ward Pharmaceuticals Corp2018-07-03Not applicableUs
Methylergonovine MaleateTablet0.2 mg/1OralPharmacist Pharmaceutical, LLC2011-08-01Not applicableUs
Methylergonovine MaleateTablet0.2 mg/1OralNovel Laboratories, Inc.2011-06-15Not applicableUs
Methylergonovine MaleateTablet0.2 mg/1OralPd Rx Pharmaceuticals, Inc.2011-08-012018-08-22Us
Methylergonovine MaleateTablet0.2 mg/1OralRemedy Repack2012-07-222013-07-23Us
Methylergonovine MaleateTablet0.2 mg/1OralAmerican Health Packaging2018-11-01Not applicableUs
International/Other Brands
Basofortina (Novartis) / Bledstop (Caprifarmindo) / Demergin (Demo) / Ergogin (Cipla) / Ergomed (Medlink) / Ergomin (Alico Impex) / Ergotyl (Sandoz) / Expogin (L.B.S.) / Glomethyl (Metiska) / Ingagen-M (Inga) / Mem (Elin) / Mergot (Lloyd) / Mergotrex (Rotexmedica) / Metenarin / Metermin (Cadila) / Méthergin (Novartis) / Methergin (Novartis) / Methergine / Metherinal (Landson) / Metherspan (Opsonin) / Methovin (Kimia Farma) / Methylergobrevin (Hemofarm) / Methylergometrin (Spofa) / Metilat (Metiska) / Metiler (Adeka) / Metilergometrina (Hospira Italia) / Metrine (T P Drug) / Metrol (Simed) / Metvell (Novell) / Myomergin (Ethica Industri Farmasi) / Myometril (Oriental Chemical Works) / Neo-ergo (Oriental) / Partan M (Mochida) / Pospargin (Kalbe) / Satergin (Tablets) / Usamema (Icon) / Utergin (Svizera) / Uterine (LBS) / Uterjin (Münir Sahin) / Uterowin (Bestochem) / Utesel (Osel)
Categories
UNII
W53L6FE61V
CAS number
113-42-8
Weight
Average: 339.4314
Monoisotopic: 339.194677059
Chemical Formula
C20H25N3O2
InChI Key
UNBRKDKAWYKMIV-QWQRMKEZSA-N
InChI
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
IUPAC Name
(4R,7R)-N-[(2S)-1-hydroxybutan-2-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide
SMILES
[H][C@@]12CC3=CNC4=CC=CC(=C34)C1=C[C@H](CN2C)C(=O)N[C@@H](CC)CO

Pharmacology

Indication

For the prevention and control of excessive bleeding following vaginal childbirth

Associated Conditions
Pharmacodynamics

Methylergometrine is a semisynthetic ergot alkaloid and a derivative of ergonovine and is used for the prevention and control of postpartum and post-abortion hemorrhage. 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.

Mechanism of action

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.

TargetActionsOrganism
AD(1A) dopamine receptor
antagonist
Human
U5-hydroxytryptamine receptor 2BNot AvailableHuman
Absorption

Absorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.

Volume of distribution
  • 56.1 ± 0 L
Protein binding
Not Available
Metabolism

Hepatic, with extensive first-pass metabolism.

Route of elimination

Ergot alkaloids are mostly eliminated by hepatic metabolism and excretion, and the decrease in bioavailability following oral administration is probably a result of first-pass metabolism in the liver.

Half life

3.39 hours

Clearance
Not Available
Toxicity

Signs and symptoms of overexposure: hypertension, seizures, headache, hypotension, nausea, and vomiting.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Methylergometrine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Methylergometrine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Methylergometrine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Methylergometrine.
4-MethoxyamphetamineMethylergometrine may increase the hypertensive and vasoconstricting activities of 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Methylergometrine.
5-methoxy-N,N-dimethyltryptamineMethylergometrine may increase the vasoconstricting activities of 5-methoxy-N,N-dimethyltryptamine.
6-Deoxyerythronolide BThe serum concentration of Methylergometrine can be increased when it is combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Methylergometrine.
AbediterolMethylergometrine may increase the hypertensive and vasoconstricting activities of Abediterol.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014497
KEGG Drug
D00680
PubChem Compound
8226
PubChem Substance
46507746
ChemSpider
7933
BindingDB
50330860
ChEBI
92607
ChEMBL
CHEMBL1201356
Therapeutic Targets Database
DAP000978
PharmGKB
PA450461
HET
H8D
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Methylergonovine
ATC Codes
G02AB01 — MethylergometrineG02AC01 — Methylergometrine and oxytocin
PDB Entries
6dry
MSDS
Download (42.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentPostpartum Haemorrhage (PPH) / Uterine Atony / Uterine tone disorders1
1CompletedPreventionCesarean Section1
4CompletedTreatmentArterial Hypotension / Uterine Atony1
4Not Yet RecruitingTreatmentPostpartum Haemorrhage (PPH) / Uterine Atony1
4RecruitingPreventionHemorrhage1
Not AvailableCompletedPreventionEndometritis1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
  • Pharmaforce inc
Packagers
  • American Regent
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • C.B. Fleet Co. Inc.
  • Cardinal Health
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
  • Pharmaforce Inc.
  • Physicians Total Care Inc.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
Dosage forms
FormRouteStrength
Tablet, coatedOral0.2 mg/1
InjectionIntramuscular; Intravenous0.2 mg/1mL
InjectionIntravenous0.2 mg/1mL
Injection, solutionIntramuscular; Intravenous0.2 mg/1mL
TabletOral0.2 mg/1
Prices
Unit descriptionCostUnit
Methergine 0.2 mg/ml ampul7.81USD ml
Methylergonovine 0.2 mg/ml vial5.28USD ml
Methergine 0.2 mg tablet1.42USD tablet
Norforms fem deodorant suppository0.29USD suppository
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)172 °CPhysProp
water solubility25 mg/mLNot Available
logP1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.204 mg/mLALOGPS
logP1.74ALOGPS
logP1.59ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15ChemAxon
pKa (Strongest Basic)7.93ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area68.36 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity99.58 m3·mol-1ChemAxon
Polarizability38.73 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.6556
Caco-2 permeable-0.8726
P-glycoprotein substrateSubstrate0.8604
P-glycoprotein inhibitor INon-inhibitor0.874
P-glycoprotein inhibitor IINon-inhibitor0.8959
Renal organic cation transporterNon-inhibitor0.7798
CYP450 2C9 substrateNon-substrate0.8316
CYP450 2D6 substrateNon-substrate0.8979
CYP450 3A4 substrateSubstrate0.664
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8641
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8959
Ames testNon AMES toxic0.5734
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.8422
Rat acute toxicity3.5304 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9614
hERG inhibition (predictor II)Inhibitor0.5889
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Ergoline and derivatives
Sub Class
Lysergic acids and derivatives
Direct Parent
Lysergamides
Alternative Parents
Indoloquinolines / Benzoquinolines / Quinoline-3-carboxamides / Pyrroloquinolines / 3-alkylindoles / Isoindoles and derivatives / Aralkylamines / Benzenoids / Heteroaromatic compounds / Pyrroles
show 9 more
Substituents
Lysergic acid amide / Indoloquinoline / Benzoquinoline / Pyrroloquinoline / Quinoline-3-carboxamide / Quinoline / 3-alkylindole / Indole / Indole or derivatives / Isoindole or derivatives
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Reyes FD, Mozzachiodi R, Baxter DA, Byrne JH: Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist. Learn Mem. 2005 May-Jun;12(3):216-20. [PubMed:15930499]
  4. Nargeot R, Baxter DA, Patterson GW, Byrne JH: Dopaminergic synapses mediate neuronal changes in an analogue of operant conditioning. J Neurophysiol. 1999 Apr;81(4):1983-7. [PubMed:10200235]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL: Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000 Dec 5;102(23):2836-41. [PubMed:11104741]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Moubarak AS, Rosenkrans CF Jr, Johnson ZB: Modulation of cytochrome P450 metabolism by ergonovine and dihydroergotamine. Vet Hum Toxicol. 2003 Feb;45(1):6-9. [PubMed:12583687]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:45