Identification

Name
Ergonovine
Accession Number
DB01253
Type
Small Molecule
Groups
Approved
Description

An ergot alkaloid with uterine and vascular smooth muscle contractile properties.

Structure
Thumb
Synonyms
  • (6aR,9R)-7-Methyl-4,6,6a,7,8,9-hexahydro-indolo[4,3-fg]quinoline-9-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide
  • [8β(S)]-9,10-didehydro-N-(2-hydroxy-1-methylethyl)-6-methylergoline-8-carboxamide
  • 9,10-didehydro-N-(2-hydroxy-1-methylethyl)-6-methylergoline-8β(S)-carboxamide
  • 9,10-didehydro-N-(α-(hydroxymethyl)ethyl)-6-methylergoline-8-β-carboxamide
  • D-lysergic acid 1-hydroxymethylethylamide
  • D-lysergic acid-L-propanolamide
  • Ergobasine
  • Ergometrina
  • Ergometrine
  • Ergométrine
  • Ergometrinum
  • Ergonovine
  • Ergotocine
  • Margonovine
  • N-(2-Hydroxy-1-methylethyl)-D-(+)-lysergamide
  • N-(α-(hydroxymethyl)ethyl)-D-lysergamide
Product Ingredients
IngredientUNIICASInChI Key
Ergonovine maleateYMH3D0ZJWV129-51-1YREISLCRUMOYAY-IIPCNOPRSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ergonovine Maleate InjectionSolution0.25 mgIntramuscular; IntravenousTeligent Ou2016-02-19Not applicableCanada
Ergonovine Maleate InjectionSolution.25 mgIntramuscular; IntravenousHospira, Inc.1981-12-31Not applicableCanada
Ergonovine Maleate InjectionSolution0.25 mgIntramuscular; IntravenousMylan Pharmaceuticals1995-12-31Not applicableCanada
Ergonovine Maleate Injection USP, 0.25mg/mlSolution0.25 mgIntramuscular; IntravenousAlveda Pharmaceuticals Inc2010-06-01Not applicableCanada
Ergotrate Maleate Tablet 1572 0.2mgTablet.2 mgOralEli Lilly & Co. Ltd.1939-12-311998-08-04Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Ergonovine MaleateErgonovine maleate (0.2 mg/1)TabletOralPharmacist Pharmaceutical, LLC2007-01-012009-12-31Us
Ergotrate MaleateErgonovine maleate (0.2 mg/1mL)Injection, solutionIntramuscularPharmacist Pharmaceutical, LLC2006-01-012009-12-31Us
International/Other Brands
Ergotrate
Categories
UNII
WH41D8433D
CAS number
60-79-7
Weight
Average: 325.4048
Monoisotopic: 325.179026995
Chemical Formula
C19H23N3O2
InChI Key
WVVSZNPYNCNODU-XTQGRXLLSA-N
InChI
InChI=1S/C19H23N3O2/c1-11(10-23)21-19(24)13-6-15-14-4-3-5-16-18(14)12(8-20-16)7-17(15)22(2)9-13/h3-6,8,11,13,17,20,23H,7,9-10H2,1-2H3,(H,21,24)/t11-,13+,17+/m0/s1
IUPAC Name
(4R,7R)-N-[(2S)-1-hydroxypropan-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](C)CO

Pharmacology

Indication

Used to treat postpartum haemorrhage and postabortion haemorrhage in patients with uterine atony.

Associated Conditions
Pharmacodynamics

Ergonovine belongs to the group of medicines known as ergot alkaloids. These medicines are usually given to stop excessive bleeding that sometimes occurs after abortion or a baby is delivered. They work by causing the muscle of the uterus to contract.

Mechanism of action

Ergonovine directly stimulates the uterine muscle to increase force and frequency of contractions. With usual doses, these contractions precede periods of relaxation; with larger doses, basal uterine tone is elevated and these relaxation periods will be decreased. Contraction of the uterine wall around bleeding vessels at the placental site produces hemostasis. Ergonovine also induces cervical contractions. The sensitivity of the uterus to the oxytocic effect is much greater toward the end of pregnancy. The oxytocic actions of ergonovine are greater than its vascular effects. Ergonovine, like other ergot alkaloids, produces arterial vasoconstriction by stimulation of alpha-adrenergic and serotonin receptors and inhibition of endothelial-derived relaxation factor release. It is a less potent vasoconstrictor than ergotamine. As a diagnostic aid (coronary vasospasm), ergonovine causes vasoconstriction of coronary arteries.

TargetActionsOrganism
AAlpha-1A adrenergic receptor
agonist
Human
Absorption

Absorption is rapid and complete after oral or intramuscular administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination

Thought to be eliminated by non-renal mechanisms (i.e. hepatic metabolism, excretion in feces)

Half life

t1/2 α=10 minutes; t1/2 β=2 hours

Clearance
Not Available
Toxicity

The principal symptoms of overdose are convulsions and gangrene. Other symptoms include bradycardia, confusion, diarrhoea, dizziness, dyspnoea, drowsiness, fast and/or weak pulse, miosis, hypercoagulability, loss of consciousness, nausea and vomiting, numbness and coldness of the extremities, pain in the chest, peripheral vasoconstriction, respiratory depression, rise or fall in blood pressure, severe cramping of the uterus, tachycardia, tingling, and unusual thirst.

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 Ergonovine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Ergonovine.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Ergonovine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Ergonovine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Ergonovine is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Ergonovine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Ergonovine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ergonovine.
4-MethoxyamphetamineErgonovine may increase the hypertensive and vasoconstricting activities of 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Ergonovine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015383
KEGG Drug
D07905
KEGG Compound
C07543
PubChem Compound
443884
PubChem Substance
46506922
ChemSpider
391970
BindingDB
50390991
ChEBI
4822
ChEMBL
CHEMBL119443
Therapeutic Targets Database
DAP000227
PharmGKB
PA449487
Drugs.com
Drugs.com Drug Page
Wikipedia
Ergonovine
ATC Codes
G02AB03 — Ergometrine
AHFS Codes
  • 76:00.00 — Oxytocics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentPost Partum Hemorrhage2
Not AvailableCompletedTreatmentPostpartum Haemorrhage (PPH)2
Not AvailableRecruitingPreventionCesarean Section Complications1
Not AvailableRecruitingTreatmentPostpartum Haemorrhage (PPH)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bioniche Pharma
  • Direct Dispensing Inc.
  • Diversified Healthcare Services Inc.
  • Laboratoires Sterop SA
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Co. Jelfa SA
  • Pharmacia Inc.
  • Prometic Pharma Inc.
  • Spectrum Pharmaceuticals
  • Valesco Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
TabletOral0.2 mg/1
SolutionIntramuscular; Intravenous.25 mg
SolutionIntramuscular; Intravenous0.25 mg
Injection, solutionIntramuscular0.2 mg/1mL
TabletOral.2 mg
Prices
Unit descriptionCostUnit
Ergonovine maleate 100% powder676.9USD g
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)162 °CPhysProp
water solubility2.68 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP0.9Not Available
pKa6.8MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.321 mg/mLALOGPS
logP1.53ALOGPS
logP1.07ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)15ChemAxon
pKa (Strongest Basic)7.93ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area68.36 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity95.05 m3·mol-1ChemAxon
Polarizability36.54 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9967
Blood Brain Barrier+0.6971
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8385
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.7295
CYP450 2C9 substrateNon-substrate0.8097
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateSubstrate0.6814
CYP450 1A2 substrateNon-inhibitor0.7284
CYP450 2C9 inhibitorNon-inhibitor0.9116
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9228
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9236
Ames testNon AMES toxic0.5743
CarcinogenicityNon-carcinogens0.9353
BiodegradationNot ready biodegradable0.8714
Rat acute toxicity3.3967 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.954
hERG inhibition (predictor II)Inhibitor0.5624
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
tertiary amino compound, organic heterotetracyclic compound, monocarboxylic acid amide, secondary amino compound, ergot alkaloid, primary alcohol (CHEBI:4822) / Indole alkaloids (C07543)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Gibson A, Carvajal A: Agonist profile of ergometrine (ergonovine) on a population of postsynaptic alpha-adrenoceptors. J Pharm Pharmacol. 1988 Feb;40(2):137-9. [PubMed:2897449]
  2. Zhu F, Han B, Kumar P, Liu X, Ma X, Wei X, Huang L, Guo Y, Han L, Zheng C, Chen Y: Update of TTD: Therapeutic Target Database. Nucleic Acids Res. 2010 Jan;38(Database issue):D787-91. doi: 10.1093/nar/gkp1014. Epub 2009 Nov 20. [PubMed:19933260]

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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. 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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. [PubMed:11961113]
  2. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267]

Drug created on April 04, 2007 16:45 / Updated on November 14, 2018 12:51