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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
SynonymLanguageCode
9,10-Didehydro-N-[1-(hydroxymethyl)-propyl]-D-lysergamideNot AvailableIUPAC
D-lysergic acid 1-butanolamideNot AvailableNot Available
ErgotylNot AvailableNot Available
MethergineNot AvailableNot Available
MethylergobasinNot AvailableNot Available
MethylergometrinGermanINN
MéthylergométrineFrenchDCF
MethylergometrineNot AvailableBAN
MethylergometrinumLatinINN
MethylergonovineNot AvailableNot Available
MetilergometrinaNot AvailableDCIT
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methergineinjection, solution.2 mg/mLintramuscular; intravenousNovartis Pharmaceuticals Corporation2002-01-282015-03-01Us
Metherginetablet, coated.2 mgoralApotheca, Inc.2006-12-27Not AvailableUs
Metherginetablet, coated.2 mgoralPd Rx Pharmaceuticals, Inc.1946-11-19Not AvailableUs
Metherginetablet, coated.2 mgoralPd Rx Pharmaceuticals, Inc.1946-11-19Not AvailableUs
Metherginetablet, coated.2 mgoralbryant ranch prepack1946-11-19Not AvailableUs
Metherginetablet, coated.2 mgoralDispensing Solutions, Inc.1946-11-19Not AvailableUs
Generic Prescription ProductsNot Available
Over the Counter ProductsNot 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
CAS number113-42-8
WeightAverage: 339.4314
Monoisotopic: 339.194677059
Chemical FormulaC20H25N3O2
InChI KeyUNBRKDKAWYKMIV-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
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.
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 substrateNon-inhibitor0.9071
CYP450 2D6 substrateInhibitor0.8931
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-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
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Pharmaforce inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionintramuscular; intravenous.2 mg/mL
Tablet, coatedoral.2 mg
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
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesG02AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (42.8 KB)
Interactions
Drug Interactions
Drug
AlmotriptanPossible severe and prolonged vasoconstriction
AtazanavirIncreases the effect and toxicity of ergot derivative
DelavirdineThe antiretroviral agent may increase the ergot derivative toxicity
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EfavirenzThe antiretroviral agent may increase the ergot derivative toxicity
EletriptanPossible severe and prolonged vasoconstriction
EpinephrinePossible marked increase of arterial pressure
ErythromycinPossible ergotism and severe ischemia with this combination
FrovatriptanPossible severe and prolonged vasoconstriction
Isosorbide DinitratePossible antagonism of action
Isosorbide MononitratePossible antagonism of action
NaratriptanPossible severe and prolonged vasocontriction
NitroglycerinPossible antagonism of action
Pentaerythritol TetranitratePossible antagonism of action
PhenylephrinePossible marked increase of arterial pressure
TelithromycinTelithromycin may reduce clearance of Methylergonovine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Methylergonovine if Telithromycin is initiated, discontinued or dose changed.
TipranavirTipranavir, co-administered with Ritonavir, may increase the plasma concentration of Methylergonovine. Concomitant therapy is contraindicated.
TramadolIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TranylcypromineIncreased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of methylergonovine by decreasing its metabolism. Concomitant therapy is contraindicated.
ZolmitriptanConcomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, methylergonovine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
Food InteractionsNot Available

Targets

1. D(1A) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(1A) dopamine receptor P21728 Details

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
  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
  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
  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
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

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Drug created on June 13, 2005 07:24 / Updated on February 04, 2014 21:00