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Identification
NameErgonovine
Accession NumberDB01253
Typesmall molecule
Groupsapproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
(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)-amideNot AvailableNot Available
[8beta(S)]-9,10-Didehydro-N-(2-hydroxy-1-methylethyl)-6-methylergoline-8-carboxamideNot AvailableNot Available
9,10-Didehydro-N-(2-hydroxy-1-methylethyl)-6-methylergoline-8beta(S)-carboxamideNot AvailableNot Available
9,10-Didehydro-N-(alpha-(hydroxymethyl)ethyl)-6-methylergoline-8-beta-carboxamideNot AvailableNot Available
D-Lysergic acid 1-hydroxymethylethylamideNot AvailableNot Available
D-Lysergic acid-L-propanolamideNot AvailableNot Available
ErgobasineNot AvailableNot Available
ErgometrinaNot AvailableNot Available
ErgometrineNot AvailableINN
ErgometrinumNot AvailableNot Available
ErgonovineNot AvailableNot Available
Ergotrate maleateNot AvailableNot Available
N-(2-Hydroxy-1-methylethyl)-D(+)-lysergamideNot AvailableNot Available
N-(alpha-(Hydroxymethyl)ethyl)-D-lysergamideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ErgotrateNot Available
Brand mixturesNot Available
Categories
CAS number60-79-7
WeightAverage: 325.4048
Monoisotopic: 325.179026995
Chemical FormulaC19H23N3O2
InChI KeyWVVSZNPYNCNODU-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[7.6.1.0^{2,7}.0^{12,16}]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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassIndoloquinolines
Direct parentIndoloquinolines
Alternative parentsBenzoquinolines; Quinoline Carboxamides; Pyrroloquinolines; N-substituted Nicotinamides; Indoles; Isoindoles and Derivatives; Tetrahydropyridines; Benzene and Substituted Derivatives; Pyrroles; Secondary Carboxylic Acid Amides; Tertiary Amines; Primary Alcohols; Enolates; Carboxylic Acids; Polyamines; Ergoline Derivatives
Substituentsbenzoquinoline; quinoline-3-carboxamide; pyrroloquinoline; n-substituted nicotinamide; isoindole or derivative; indole; indole or derivative; tetrahydropyridine; benzene; pyrrole; tertiary amine; carboxamide group; secondary carboxylic acid amide; primary alcohol; carboxylic acid derivative; polyamine; carboxylic acid; enolate; alcohol; organonitrogen compound; amine
Classification descriptionThis compound belongs to the indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
Pharmacology
IndicationUsed to treat postpartum haemorrhage and postabortion haemorrhage in patients with uterine atony.
PharmacodynamicsErgonovine 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 actionErgonovine 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.
AbsorptionAbsorption is rapid and complete after oral or intramuscular administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationThought to be eliminated by non-renal mechanisms (i.e. hepatic metabolism, excretion in feces)
Half lifet1/2 α=10 minutes; t1/2 β=2 hours
ClearanceNot Available
ToxicityThe 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9967
Blood Brain Barrier + 0.6971
Caco-2 permeable - 0.8957
P-glycoprotein substrate Substrate 0.8385
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.8382
Renal organic cation transporter Non-inhibitor 0.7295
CYP450 2C9 substrate Non-substrate 0.8097
CYP450 2D6 substrate Non-substrate 0.9115
CYP450 3A4 substrate Substrate 0.6814
CYP450 1A2 substrate Non-inhibitor 0.7284
CYP450 2C9 substrate Non-inhibitor 0.9116
CYP450 2D6 substrate Inhibitor 0.8931
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.9228
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9236
Ames test Non AMES toxic 0.5743
Carcinogenicity Non-carcinogens 0.9353
Biodegradation Not ready biodegradable 0.8714
Rat acute toxicity 3.3967 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.954
hERG inhibition (predictor II) Inhibitor 0.5624
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
SolutionIntramuscular0.2 mg/ml
SolutionIntramuscular0.25 mg/ml
TabletOral0.2 mg
Prices
Unit descriptionCostUnit
Ergonovine maleate 100% powder676.9USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point162 °CPhysProp
water solubility2.68 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP0.9Not Available
pKa6.8MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
water solubility3.21e-01 g/lALOGPS
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 area68.36ChemAxon
rotatable bond count3ChemAxon
refractivity95.05ChemAxon
polarizability36.54ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07543
PubChem Compound443884
PubChem Substance46506922
ChemSpider391970
ChEBI4822
ChEMBLCHEMBL119443
Therapeutic Targets DatabaseDAP000227
PharmGKBPA449487
Drug Product Database497312
Drugs.comhttp://www.drugs.com/cdi/ergonovine.html
WikipediaErgonovine
ATC CodesG02AB03
AHFS Codes
  • 76:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcebutololIschemia with risk of gangrene
AlmotriptanPossible severe and prolonged vasoconstriction
AtenololIschmeia with risk of gangrene
BisoprololIschemia with risk of gangrene
CarvedilolIschemia with risk of gangrene
DelavirdineThe antiretroviral agent may increase the ergot derivative toxicity
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EfalizumabThe antiretroviral agent may increase the ergot derivative
EletriptanPossible severe and prolonged vasoconstriction
EpinephrinePossible marked increase of arterial pressure
ErythromycinPossible ergotism and severe ischemia with this combination
EsmololIschemia with risk of gangrene
FrovatriptanPossible severe and prolonged vasoconstriction
Isosorbide DinitratePossible antagonism of action
Isosorbide MononitratePossible antagonism of action
LabetalolIschemia with risk of gangrene
MetoprololIschemia with risk of gangrene
NadololIschemia with risk of gangrene
NaratriptanPossible severe and prolonged vasocontriction
NitroglycerinPossible antagonism of action
OxprenololIschemia with risk of gangrene
Pentaerythritol TetranitratePossible antagonism of action
PhenylephrinePossible marked increase of arterial pressure
PindololIschemia with risk of gangrene
PropranololIschemia with risk of gangrene
TelithromycinTelithromycin may reduce clearance of Ergonovine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Ergonivine if Telithromycin is initiated, discontinued or dose changed.
TimololIschemia with risk of gangrene
TipranavirTipranavir, co-administered with Ritonavir, may increase the plasma concentration of Ergonovine. 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 ergonovine by decreasing its metabolism. Concomitant therapy is contraindicated.
ZolmitriptanConcomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, ergonovine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
Food InteractionsNot Available

Targets

1. Alpha-1A adrenergic receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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
  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. Epub 2009 Nov 20. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed
  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

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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
  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

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Drug created on April 04, 2007 16:45 / Updated on September 16, 2013 17:13