Banner
targets (1) enzymes (1)
for drugs
Identification
Name Methylergonovine
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Methylergobasin
  • Methylergobasine
  • Methylergobrevin
  • Methylergometrin
  • Methylergometrine
  • Methylergonovin
  • methylergonovine maleate
Brand names
  • Basofortina
  • Metenarin
  • Methergen
  • Methergin
  • Methergine
  • Norforms
  • Partergin
  • Ryegonovin
  • Spametrin-M
Brand name mixtures Not Available
Categories
  • Oxytocics
CAS number 113-42-8
Weight Average: 339.4314
Monoisotopic: 339.194677059
Chemical Formula C20H25N3O2
InChI Key InChIKey=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
Plain Text
IUPAC Name
(4R,7R)-N-[(2S)-1-hydroxybutan-2-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaene-4-carboxamide
SMILES
[H][C@@]12CC3=CNC4=C3C(=CC=C4)C1=C[C@H](CN2C)C(=O)N[C@@H](CC)CO
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Ergolines
  • Indoloquinolines
Substructures
  • Ergolines
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Indoles and Indole Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Pyrroles
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Aliphatic and Aryl Amines
  • Isoprenes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Tryptamines and Derivatives
  • Amphetamines
  • Indoloquinolines
Pharmacology
Indication For the prevention and control of excessive bleeding following vaginal childbirth
Pharmacodynamics Methylergonovine 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 Methylergonovine 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.
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
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Pharmaforce inc
Packagers
Dosage forms
Form Route Strength
Solution Intramuscular
Solution Intravenous
Tablet Oral
Prices
Unit description Cost Unit
Methergine 0.2 mg/ml ampul 7.81 USD ml
Methylergonovine 0.2 mg/ml vial 5.28 USD ml
Methergine 0.2 mg tablet 1.42 USD tablet
Norforms fem deodorant suppository 0.29 USD suppository
Patents Not Available
Properties
State solid
Melting point 172 oC
Experimental Properties
Property Value Source
water solubility 25 mg/mL PhysProp
logP 1.2 PhysProp
Predicted Properties
Property Value Source
water solubility 2.04e-01 g/l ALOGPS
logP 1.74 ALOGPS
logP 1.59 ChemAxon Molconvert
logS -3.22 ALOGPS
pKa 15.95 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 68.36 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 99.58 ChemAxon Molconvert
polarizability 38.73 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00680 Link_out
PubChem Compound 8226 Link_out
PubChem Substance 46507746 Link_out
ChemSpider 7933 Link_out
Therapeutic Targets Database DAP000978 Link_out
PharmGKB PA450460 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic2/methylerg.htm Link_out
Drugs.com http://www.drugs.com/cdi/methylergonovine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/met1256.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Methylergonovine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (42.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. D(1A) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase

Organism class: human
UniProt ID: P21728 Link_out
Gene: DRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on May 04, 2011 12:50

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.