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Record Information
Version2.0
Creation Date2010-04-21 19:31:18 UTC
Update Date2014-12-24 20:26:22 UTC
Accession NumberT3D3686
Identification
Common NameMethylergonovine
ClassSmall Molecule
DescriptionMethylergonovine is only found in individuals that have used or taken this drug. It is a homolog of ergonovine containing one more CH2 group (Merck Index, 11th ed). 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.
Compound Type
  • Amide
  • Amine
  • Drug
  • Metabolite
  • Organic Compound
  • Oxytocic
  • Serotonin Antagonist
  • Synthetic Compound
  • Vasoconstrictor Agent
Chemical Structure
Thumb
Synonyms
Synonym
9,10-Didehydro-N-[1-(hydroxymethyl)-propyl]-D-lysergamide
Basofortina
Bledstop
D-lysergic acid 1-butanolamide
Demergin
Ergogin
Ergomed
Ergomin
Ergotyl
Expogin
Glomethyl
Ingagen-M
Mem
Mergot
Mergotrex
Metenarin
Metermin
Méthergin
Methergine
Metherinal
Metherspan
Methovin
Methylergobasin
Methylergobasine
Methylergobrevin
Methylergometrin
Methylergometrine
Methylergometrinum
Methylergonovin
Methylergonovine maleate
Metilat
Metiler
Metilergometrina
Metrine
Metrol
Metvell
Myomergin
Myometril
Neo-ergo
Partan M
Pospargin
Satergin
Usamema
Utergin
Uterine
Uterjin
Uterowin
Utesel
Chemical FormulaC20H25N3O2
Average Molecular Mass339.431 g/mol
Monoisotopic Mass339.195 g/mol
CAS Registry Number113-42-8
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
Traditional Namemethylergonovine
SMILES[H][C@](CC)(CO)N=C(O)[C@@]1([H])CN(C)[C@]2([H])CC3=CNC4=CC=CC(=C34)C2=C1
InChI IdentifierInChI=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
InChI KeyInChIKey=UNBRKDKAWYKMIV-QWQRMKEZSA-N
Chemical Taxonomy
Description 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
  • Pyrroloquinoline
  • Quinoline-3-carboxamide
  • Quinoline
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • Isoindole or derivatives
  • Aralkylamine
  • Benzenoid
  • Heteroaromatic compound
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Amino acid or derivatives
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Alcohol
  • Organonitrogen compound
  • Organooxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Primary alcohol
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point172°C
Boiling PointNot Available
Solubility25 mg/mL
LogP1.2
Predicted Properties
PropertyValueSource
Water Solubility0.2 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity99.58 m³·mol⁻¹ChemAxon
Polarizability38.73 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-3914000000-d6349f005e3253821421JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-01ba-4095000000-07cac91c483c45e0b4fcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-006x-1019000000-5743eb114639a8b4cd68JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uk9-4093000000-2f215482a3bef9973b4fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-3940000000-bf7ef321bb426974d49bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0019000000-25ad156f1bdbadfdb37fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-05g0-2169000000-04eae81fd7d7bb4dbf72JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05fu-8290000000-0f17abb269c859d8cdacJSpectraViewer
Toxicity Profile
Route of ExposureIngestion (6). Absorption is rapid after oral (60% bioavailability) and intramuscular (78% bioavailability) administration.
Mechanism of ToxicityErgoline alkaloids have been shown to have the significant affinity towards the 5-HT1 and 5-HT2 serotonin receptors, D1 and D2 dopamine receptors, and alpha-adrenergic receptors. This can result in a number of different effects, including vasoconstriction, convulsions, and hallucinations. (2, 3, 4)
MetabolismHepatic, 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMethylergometrine is a synthetic analogue of ergonovine, an alkaloid of the ergoline family that occurs in various species of vines of the Convolvulaceae (morning glory) family and in some species of lower fungi like other ergoline alkaloids. Methylergometrine is a blood vessel constrictor and smooth muscle agonist most commonly used to prevent or control excessive bleeding following childbirth and spontaneous or elective abortion. It also causes uterine contractions to aid in expulsion of retained products of conception after a missed abortion (miscarriage in which all or part of the fetus remains in the uterus) and to help deliver the placenta after childbirth. The drug is currently prepared via reaction of (+)-lysergic acid with L-(+)-aminobutanol, using different coupling reagents, and is available under the name Methergine as tablets or injection (IM or IV) or in liquid form to be taken orally. (5, 8)
Minimum Risk LevelNot Available
Health EffectsIngestion of ergoline alkaloids is known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (1)
SymptomsConvulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (6)
TreatmentTreatment for ergotism consists of vasodilators, anticoagulants and low molecular weight dextrans. If necessary, a sympathetic nerve blockade may be carried out, such as brachial plexus blockade. Temporary sedation (e.g. haloperidol) will be necessary in hallucination and diazepam is used for convulsions. There is no specific antidote. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00353
HMDB IDHMDB14497
PubChem Compound ID8226
ChEMBL IDCHEMBL1201356
ChemSpider ID7933
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID775307
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkMethylergonovine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Richard JL: Some major mycotoxins and their mycotoxicoses--an overview. Int J Food Microbiol. 2007 Oct 20;119(1-2):3-10. Epub 2007 Jul 31. [17719115 ]
  2. Mantegani S, Brambilla E, Varasi M: Ergoline derivatives: receptor affinity and selectivity. Farmaco. 1999 May 30;54(5):288-96. [10418123 ]
  3. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
  4. Kvernmo T, Hartter S, Burger E: A review of the receptor-binding and pharmacokinetic properties of dopamine agonists. Clin Ther. 2006 Aug;28(8):1065-78. [16982285 ]
  5. Wikipedia. Ergoline. Last Updated 2 April 2010. [Link]
  6. Wikipedia. Ergotism. Last Updated 6 April 2010. [Link]
  7. Van den Enden, E. (2004). Illustrated Lecture Notes on Tropical Medicine. [Link]
  8. Wikipedia. Methylergometrine. Last Updated 13 April 2010. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. [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. [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. [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. [10200235 ]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.
Gene Name:
HTR2B
Uniprot ID:
P41595
Molecular Weight:
54297.41 Da
References
  1. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
  2. 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. [11104741 ]
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
References
  1. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
References
  1. Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]