|Systematic (IUPAC) name|
|(6aR,9R)-N-((2R,5S,10aS,10bS)- 5-benzyl-10b-hydroxy-2-methyl- 3,6-dioxooctahydro-2H-oxazolo[3,2-a] pyrrolo[2,1-c]pyrazin-2-yl) -7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg] quinoline-9-carboxamide|
|Trade names||Cafergot, Ergomar|
Oral: <1%  (Enhanced by co-administration of caffeine )
|Half-life||2 hours |
|Excretion||90% biliary |
|Mol. mass||581.66 g/mol|
|(what is this?)|
Ergotamine is an ergopeptine and part of the ergot family of alkaloids; it is structurally and biochemically closely related to ergoline. It possesses structural similarity to several neurotransmitters, and has biological activity as a vasoconstrictor.
It is used medicinally for treatment of acute migraine attacks (sometimes in combination with caffeine). Medicinal usage of ergot fungus began in the 16th century to induce childbirth, yet dosage uncertainties discouraged the use. It has been used to prevent post-partum haemorrhage (bleeding after childbirth). It was first isolated from the ergot fungus by Arthur Stoll at Sandoz in 1918 and marketed as Gynergen in 1921.
Mechanism of action
The mechanism of action of ergotamine is complex. The molecule shares structural similarity with neurotransmitters such as serotonin, dopamine, and epinephrine and can thus bind to several receptors acting as an agonist. The anti-migraine effect is due to constriction of the intracranial extracerebral blood vessels through the 5-HT1B receptor, and by inhibiting trigeminal neurotransmission by 5-HT1D receptors. Ergotamine also has effects on the dopamine and norepinephrine receptors. Its side effects are due mainly to its action at the D2 dopamine and 5-HT1A receptors.
Ergotamine is a secondary metabolite (natural product) and the principal alkaloid produced by the ergot fungus, Claviceps purpurea, and related fungi in the family Clavicipitaceae. Its biosynthesis in these fungi requires the amino acid L-tryptophan and dimethylallyl diphosphate. These precursor compounds are the substrates for the enzyme, dimethylallyl-tryptophan (DMAT) synthase, catalyzing the first step in ergot alkaloid biosynthesis, i.e., the prenylation of L-tryptophan. Further reactions, involving methyltransferase and oxygenase enzymes, yield the ergoline, lysergic acid. Lysergic acid (LA) is the substrate of lysergyl peptide synthetase, a nonribosomal peptide synthetase, which covalently links LA to the amino acids, L-alanine, L-proline, and L-phenylalanine. Enzyme-catalyzed or spontaneous cyclizations, oxygenations/oxidations, and isomerizations at selected residues precede, and give rise to, formation of ergotamine.
Ergotamine produces vasoconstriction peripherally as well as damages the peripheral epithelium. In high doses ergotamine is conducive to vascular stasis, thrombosis and gangrene. It can increase uterine contractivity and occasionally is used therapeutically immediately post-partum to decrease uterine bleeding. See also ergometrine.
Ergotamine continues to be prescribed for migraines.
Availability and dosage
In the United States, ergotamine is available as a suppository, a sublingual tablet, and a tablet in combination with caffeine. The suppository is available under the brand name Miegerot, which contains 2 mg of ergotamine with 100 mg caffeine. The sublingual tablet is available under the brand name Ergomar and contains 2 mg of ergotamine. The combination tablet in combination with caffeine called Cafergot contains 1 mg of ergotamine and 100 mg of caffeine.
Cafergot is no longer commercially available.
- Cafergot, an abortive migraine treatment with ergotamine and caffeine
- Dihydroergotamine, a semi-synthetic form used as an abortive migraine treatment
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- Pharmacognosy of Ergot
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- FDA Orange Book http://www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm