Ergonovine
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Basic Info
| Common Name | Ergonovine(F04933) |
| 2D Structure | |
| Description | Ergonovine is only found in individuals that have used or taken this drug. It is an ergot alkaloid with uterine and vascular smooth muscle contractile properties. [PubChem] 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. |
| FRCD ID | F04933 |
| CAS Number | 60-79-7 |
| PubChem CID | 443884 |
| Formula | C19H23N3O2 |
| IUPAC Name | (6aR,9R)-N-[(2S)-1-hydroxypropan-2-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide |
| 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 |
| Canonical SMILES | CC(CO)NC(=O)C1CN(C2CC3=CNC4=CC=CC(=C34)C2=C1)C |
| Isomeric SMILES | C[C@@H](CO)NC(=O)[C@H]1CN([C@@H]2CC3=CNC4=CC=CC(=C34)C2=C1)C |
| Wikipedia | Ergonovine |
| Synonyms |
Ergometrinum
ERGONOVINE
Ergometrine
Ergobasine
Ergotocine
Ergometrin
Margonovine
Ergometrina
Ergostetrine
Ergotrate
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Alkaloids and derivatives |
| Class | Ergoline and derivatives |
| Subclass | Lysergic acids and derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Lysergamides |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| 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 |
| Description | This compound belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 325.412 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 3 |
| Complexity | 535 |
| Monoisotopic Mass | 325.179 |
| Exact Mass | 325.179 |
| XLogP | 1.8 |
| Formal Charge | 0 |
| Heavy Atom Count | 24 |
| Defined Atom Stereocenter Count | 3 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.6971 |
| Human Intestinal Absorption | HIA+ | 0.9967 |
| Caco-2 Permeability | Caco2- | 0.8957 |
| P-glycoprotein Substrate | Substrate | 0.8385 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8782 |
| Non-inhibitor | 0.8382 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.7295 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5333 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8097 |
| CYP450 2D6 Substrate | Non-substrate | 0.9115 |
| CYP450 3A4 Substrate | Substrate | 0.6814 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7284 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9116 |
| CYP450 2D6 Inhibitor | Inhibitor | 0.8931 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9026 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9228 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9236 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9540 |
| Inhibitor | 0.5624 | |
| AMES Toxicity | Non AMES toxic | 0.5743 |
| Carcinogens | Non-carcinogens | 0.9353 |
| Fish Toxicity | High FHMT | 0.9684 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8696 |
| Honey Bee Toxicity | Low HBT | 0.7077 |
| Biodegradation | Not ready biodegradable | 0.8714 |
| Acute Oral Toxicity | II | 0.6619 |
| Carcinogenicity (Three-class) | Non-required | 0.6595 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.2641 | LogS |
| Caco-2 Permeability | 0.7084 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.3967 | LD50, mol/kg |
| Fish Toxicity | 1.3828 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.2642 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Detection of Total Ergot Alkaloids in Cereal Flour and in Bread by a Generic Enzyme Immunoassay Method. | J AOAC Int | 2018 May 1 | 28964275 |
| Localization of ergot alkaloids in sclerotia of Claviceps purpurea by matrix-assisted laser desorption/ionization mass spectrometry imaging. | Anal Bioanal Chem | 2017 Feb | 27873003 |
| Toxic effects, metabolism, and carry-over of ergot alkaloids in laying hens, with a special focus on changes of the alkaloid isomeric ratio in feed caused by hydrothermal treatment. | Mycotoxin Res | 2016 Feb | 26809637 |
| Ergot alkaloids in feed for Pekin ducks: toxic effects, metabolism and carry over into edible tissues. | Toxins (Basel) | 2015 Jun 2 | 26043275 |
| Uterotonic drug quality: an assessment of the potency of injectable uterotonicdrugs purchased by simulated clients in three districts in Ghana. | BMJ Open | 2012 May 3 | 22556159 |
| Constriction of bovine vasculature caused by endophyte-infected tall fescue seed extract is similar to pure ergovaline. | J Anim Sci | 2012 May | 22147482 |
| Permeability of ergot alkaloids across the blood-brain barrier in vitro andinfluence on the barrier integrity. | Mol Nutr Food Res | 2012 Mar | 22147614 |
| Effect of ergot alkaloids on contractility of bovine right ruminal artery and vein. | J Anim Sci | 2011 Sep | 21512122 |
| Indole-diterpenes and ergot alkaloids in Cynodon dactylon (Bermuda grass) infected with Claviceps cynodontis from an outbreak of tremors in cattle. | J Agric Food Chem | 2009 Dec 9 | 19891432 |
| Ergot alkaloids in rye flour determined by solid-phase cation-exchange andhigh-pressure liquid chromatography with fluorescence detection. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2008Mar | 18311624 |
| Effects of the ergot alkaloids dihydroergotamine, ergonovine, and ergotamine ongrowth of Escherichia coli O157:H7 in vitro. | Foodborne Pathog Dis | 2008 Oct | 18681792 |
| Determination of ergot alkaloids: purity and stability assessment of standardsand optimization of extraction conditions for cereal samples. | J AOAC Int | 2008 Nov-Dec | 19202797 |
| Simultaneous determination of six major ergot alkaloids and their epimers incereals and foodstuffs by LC-MS-MS. | Anal Bioanal Chem | 2008 May | 18415090 |
| Determination of ergot alkaloids in feed by HPLC. | Mycotoxin Res | 2008 Jun | 23604683 |
| Electrospray[+] tandem quadrupole mass spectrometry in the elucidation of ergot alkaloids chromatographed by HPLC: screening of grass or forage samples for novel toxic compounds. | J Mass Spectrom | 2005 Nov | 16278935 |
| Semiquantitative determination of ergot alkaloids in seed, straw, and digesta samples using a competitive enzyme-linked immunosorbent assay. | J Vet Diagn Invest | 2001 May | 11482600 |
| Ergotism and photosensitization in swine produced by the combined ingestion ofClaviceps purpurea sclerotia and Ammi majus seeds. | J Vet Diagn Invest | 1997 Jan | 9087928 |
| The effect of alkaloids and seed extracts of endophyte-infected tall fescue onprolactin secretion in an in vitro rat pituitary perfusion system. | J Anim Sci | 1992 Sep | 1399895 |
| Physiological responses in rats fed extracts of endophyte-free and endophyte-infected tall fescue seed relative to some known ergot alkaloids. | Drug Chem Toxicol | 1989 Jun | 2598831 |
| Toxic effects of cyclopiazonic acid in the early phase of pregnancy in mice. | Res Commun Chem Pathol Pharmacol | 1987 Mar | 3575873 |
Targets
- 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
- Mechanism of Action:
- Ergometrine acts as an agonist at 5-HT2 receptors, causing direct stimulation of the uterine smooth musculature, resulting in increased muscular tone and an enhancement of the rate and force of rhythmical contractions.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- 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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1A
- Uniprot ID:
- P35348
- Molecular Weight:
- 51486.005 Da
- Mechanism of Action:
- Ergometrine is partitally agonistic of alpha-adrenergic receptors.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- 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) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
- Gene Name:
- ADRA1B
- Uniprot ID:
- P35368
- Molecular Weight:
- 56835.375 Da
- Mechanism of Action:
- Ergometrine is partitally agonistic of alpha-adrenergic receptors.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- General Function:
- Alpha1-adrenergic receptor activity
- Specific Function:
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
- Gene Name:
- ADRA1D
- Uniprot ID:
- P25100
- Molecular Weight:
- 60462.205 Da
- Mechanism of Action:
- Ergometrine is partitally agonistic of alpha-adrenergic receptors.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- General Function:
- Thioesterase binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
- Gene Name:
- ADRA2A
- Uniprot ID:
- P08913
- Molecular Weight:
- 48956.275 Da
- Mechanism of Action:
- Ergometrine is partitally agonistic of alpha-adrenergic receptors.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- General Function:
- Epinephrine binding
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
- Gene Name:
- ADRA2B
- Uniprot ID:
- P18089
- Molecular Weight:
- 49565.8 Da
- Mechanism of Action:
- Ergometrine is partitally agonistic of alpha-adrenergic receptors.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- General Function:
- Protein homodimerization activity
- Specific Function:
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
- Gene Name:
- ADRA2C
- Uniprot ID:
- P18825
- Molecular Weight:
- 49521.585 Da
- Mechanism of Action:
- Ergometrine is partitally agonistic of alpha-adrenergic receptors.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]
- General Function:
- Potassium channel regulator activity
- Specific Function:
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
- Gene Name:
- DRD2
- Uniprot ID:
- P14416
- Molecular Weight:
- 50618.91 Da
- Mechanism of Action:
- Ergometrine acts as an agonist at the D2 dopamine receptor, inhibiting cyclic AMP production.
References
- Larson BT, Harmon DL, Piper EL, Griffis LM, Bush LP: Alkaloid binding and activation of D2 dopamine receptors in cell culture. J Anim Sci. 1999 Apr;77(4):942-7. [10328360 ]
- 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
- Mechanism of Action:
- Ergometrine acts as an agonist at 5-HT2 receptors, causing direct stimulation of the uterine smooth musculature, resulting in increased muscular tone and an enhancement of the rate and force of rhythmical contractions.
References
- 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
- Mechanism of Action:
- Ergometrine acts as an agonist at 5-HT2 receptors, causing direct stimulation of the uterine smooth musculature, resulting in increased muscular tone and an enhancement of the rate and force of rhythmical contractions.
References
- Schiff PL: Ergot and its alkaloids. Am J Pharm Educ. 2006 Oct 15;70(5):98. [17149427 ]