(4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide

• ChemBase ID: 578
• Molecular Formular: C33H35N5O5
• Molecular Mass: 581.6615
• Monoisotopic Mass: 581.26381925
• SMILES: O1[C@]2(O)N([C@H](C(=O)N3[C@H]2CCC3)Cc2ccccc2)C(=O)[C@@]1(NC(=O)[C@H]1CN([C@H]2C(=C1)c1c3c(C2)c[nH]c3ccc1)C)C
• Canonical SMILES: O=C([C@H]1CN(C)[C@H]2C(=C1)c1cccc3c1c(C2)c[nH]3)N[C@]1(C)O[C@@]2(N(C1=O)[C@@H](Cc1ccccc1)C(=O)N1[C@H]2CCC1)O
• InChI: InChI=1S/C33H35N5O5/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32/h3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39)/t21-,25-,26+,27+,32-,33+/m1/s1
• InChIKey: XCGSFFUVFURLIX-VFGNJEKYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0^2,^6]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^2,^7.0^1^2,^1^6]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide; (4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-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
• IUPAC Traditional name: ergomar; gynergen
• Brand Name: Ergomar; Ergostat; Ergotamin; Ergoton-A; Medihaler Ergotamine; Wigrettes
• Synonyms: Ergotamine

Database IDs

• CAS Number: 113-15-5
• PubChem SID: 160964041; 46507632
• PubChem CID: 8223
• CHEBI ID: 64318
• ATC CODE: N02CA02
• CHEMBL: 442
• Chemspider ID: 7930
• DrugBank ID: DB00696
• IUPHAR ligand ID: 149
• KEGG ID: D07906
• Unique Ingredient Identifier: PR834Q503T
• Wikipedia Title: Ergotamine

CALCULATED PROPERTIES

JChem

• Polarizability: 62.688698 Å^3
• Polar Surface Area: 118.21 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: false
• Acid pKa: 9.695263
• H Acceptors: 6
• H Donor: 3
• LogD (pH = 5.5): 0.44161355
• LogD (pH = 7.4): 2.1667228
• Log P: 2.5976973
• Molar Refractivity: 160.1678 cm^3

ALOGPS 2.1

• Solubility (Water): 2.23e-01 g/l
• Log P: 2.95
• LOG S: -3.42

PROPERTIES

Physical Property

• Solubility: Slight
• Hydrophobicity(logP): 2

Pharmacology Properties

• Admin Routes: Oral
• Bioavailability: Intravenous: 100%,; Intramuscular: 47%,; Oral: <1% (Enhanced by co-administration of caffeine )
• Excretion: 90% biliary
• Half Life: 2 hours
• Metabolism: Hepatic
• Legal Status: POM (UK); Rx-only (US); Schedule 4 (Australia)
• Pregnancy Category: X (US)

DETAILS

DrugBank - DB00696

• Drug Groups: approved
• Description: A vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine disorders. [PubChem]
• Indication: For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia".
• Pharmacology: Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow.
• Toxicity: Signs of overexposure include irritation, nausea, vomiting, headache, diarrhea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Ergotamine is metabolized by the liver by largely undefined pathways, and 90% of the metabolites are excreted in the bile.
• Absorption: The bioavailability of sublingually administered ergotamine has not been determined.
• Half Life: 2 hours
• References: Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ: Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000 Jan;123 ( Pt 1):9-18. [Pubmed] ; Schardl CL, Panaccione DG, Tudzynski P: Ergot alkaloids--biology and molecular biology. Alkaloids Chem Biol. 2006;63:45-86. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ: Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000 Jan;123 ( Pt 1):9-18. Pubmed
• Schardl CL, Panaccione DG, Tudzynski P: Ergot alkaloids--biology and molecular biology. Alkaloids Chem Biol. 2006;63:45-86. Pubmed