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Identification
NameMethylergometrine
Accession NumberDB00353  (APRD00739)
TypeSmall Molecule
GroupsApproved
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
Methergine
Methylergobasin
Methylergometrin
Méthylergométrine
Methylergometrine
Methylergometrinum
Methylergonovine
Metilergometrina
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Metherginetablet, coated.2 mg/1oralApotheca, Inc.2006-12-27Not applicableUs
Metherginetablet, coated.2 mg/1oralDispensing Solutions, Inc.1946-11-19Not applicableUs
Metherginetablet, coated.2 mg/1oralbryant ranch prepack1946-11-19Not applicableUs
Metherginetablet, coated.2 mg/1oralPd Rx Pharmaceuticals, Inc.1946-11-192016-04-05Us
Metherginetablet, coated.2 mg/1oralPd Rx Pharmaceuticals, Inc.1946-11-192016-04-05Us
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Metherginetablet.2 mg/1oralLupin Pharma2016-04-04Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralKAISER FOUNDATION HOSPITALS2012-05-31Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralREMEDYREPACK INC.2013-02-25Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralGAVIS Pharmaceuticals, LLC2011-06-15Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralPd Rx Pharmaceuticals, Inc.2011-08-01Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralNovel Laboratories, Inc.2011-06-15Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralAmerican Health Packaging2012-05-01Not applicableUs
Methylergonovine Maleateinjection.2 mg/mLintramuscular; intravenousAkorn, Inc.2011-03-02Not applicableUs
Methylergonovine Maleatetablet.2 mg/1oralPharmacist Pharmaceutical, LLC2011-08-01Not applicableUs
Methylergonovine Maleateinjection, solution.2 mg/mLintramuscular; intravenousAmerican Regent, Inc.2010-06-21Not applicableUs
Methylergonovine Maleateinjection, solution.2 mg/mLintramuscular; intravenousPharmacist Pharmaceutical, LLC2010-11-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BasofortinaNovartis
BledstopCaprifarmindo
DemerginDemo
ErgoginCipla
ErgomedMedlink
ErgominAlico Impex
ErgotylSandoz
ExpoginL.B.S.
GlomethylMetiska
Ingagen-MInga
MemElin
MergotLloyd
MergotrexRotexmedica
MetenarinNot Available
MeterminCadila
MétherginNovartis
MetherginNovartis
MetherinalLandson
MetherspanOpsonin
MethovinKimia Farma
MethylergobrevinHemofarm
MethylergometrinSpofa
MetilatMetiska
MetilerAdeka
MetilergometrinaHospira Italia
MetrineT P Drug
MetrolSimed
MetvellNovell
MyomerginEthica Industri Farmasi
MyometrilOriental Chemical Works
Neo-ergoOriental
Partan MMochida
PosparginKalbe
SaterginTablets
UsamemaIcon
UterginSvizera
UterineLBS
UterjinMünir Sahin
UterowinBestochem
UteselOsel
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Methylergometrine maleate
ThumbNot applicableDBSALT001025
Methylergonovine tartrate
ThumbNot applicableDBSALT001062
Categories
UNIIW53L6FE61V
CAS number113-42-8
WeightAverage: 339.4314
Monoisotopic: 339.194677059
Chemical FormulaC20H25N3O2
InChI KeyInChIKey=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[[email protected]](CN2C)C(=O)N[C@@H](CC)CO
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassErgoline and derivatives
Sub ClassLysergic acids and derivatives
Direct ParentLysergamides
Alternative Parents
Substituents
  • Lysergic acid amide
  • Indoloquinoline
  • Benzoquinoline
  • Quinoline-3-carboxamide
  • Pyrroloquinoline
  • Quinoline
  • Isoindole or derivatives
  • Indole or derivatives
  • Indole
  • Aralkylamine
  • Tetrahydropyridine
  • Benzenoid
  • Heteroaromatic compound
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the prevention and control of excessive bleeding following vaginal childbirth
PharmacodynamicsMethylergometrine 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 actionMethylergometrine 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.
Related Articles
AbsorptionAbsorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.
Volume of distribution
  • 56.1 ± 0 L
Protein bindingNot Available
Metabolism

Hepatic, with extensive first-pass metabolism.

Route of eliminationErgot 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 life3.39 hours
ClearanceNot Available
ToxicitySigns and symptoms of overexposure: hypertension, seizures, headache, hypotension, nausea, and vomiting.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Pharmaforce inc
Packagers
Dosage forms
FormRouteStrength
Tablet, coatedoral.2 mg/1
Injectionintramuscular; intravenous.2 mg/mL
Injection, solutionintramuscular; intravenous.2 mg/mL
Tabletoral.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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point172 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesG02AC01G02AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (42.8 KB)
Interactions
Drug Interactions
Drug
BoceprevirThe serum concentration of Methylergometrine can be increased when it is combined with Boceprevir.
CobicistatThe serum concentration of Methylergometrine can be increased when it is combined with Cobicistat.
ItraconazoleThe serum concentration of Methylergometrine can be increased when it is combined with Itraconazole.
KetoconazoleThe serum concentration of Methylergometrine can be increased when it is combined with Ketoconazole.
PosaconazoleThe serum concentration of Methylergometrine can be increased when it is combined with Posaconazole.
TelaprevirThe serum concentration of Methylergometrine can be increased when it is combined with Telaprevir.
VoriconazoleThe serum concentration of Methylergometrine can be increased when it is combined with Voriconazole.
Food InteractionsNot 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
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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23