Ergotamine


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. 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 hemorrhage. 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 5-hydroxytryptamine receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5-HT, 5-HT, and 5-HT receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the "triptan" sumatriptan, are all agonists for these receptors. Ergotamine and DHE were originally developed as sympatholytics, but it was later concluded that their therapeutic efficacy was probably mediated by vasoconstriction of cranial blood vessels. As expected
from this pharmacologic profile, their most important pharmacologic effect is arterial constriction.

Biosynthesis

Ergotamine is a secondary metabolite 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, tryptophan dimethylallyltransferase, 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 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.

Medical use

Ergotamine continues to be prescribed for migraines and cluster headaches.

Contraindications

Contraindications include: atherosclerosis, Buerger's syndrome, coronary artery disease, hepatic disease, pregnancy, pruritus, Raynaud's syndrome, and renal disease.
It's also contraindicated if patient is taking macrolide antibiotics, certain HIV protease inhibitors, certain azole antifungals delavirdine, efavirenz or a 5-HT1 agonist.

Availability and dosage

In the United States, ergotamine is available as a suppository, a sublingual tablet, and a tablet, sometimes in combination with caffeine. The suppository is available under the brand name Migergot, 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.
This preparation may be used immediately following the aura/onset of pain to abort the migraine. For the best results, dosage should start at the first sign of an attack.

Side effects

Side effects of ergotamine include nausea and vomiting. At higher doses, it can cause raised arterial blood pressure, vasoconstriction and bradycardia or tachycardia. Severe vasoconstriction may cause symptoms of intermittent claudication.

Legal status

Ergotamine is a controlled substance in the United States as it is a commonly used precursor for the production of LSD.