Ergotamine

Ergotamine is indicated as therapy to abort or prevent vascular headache. Available forms Ergotamine is available as a suppository and as a tablet, sometimes in combination with caffeine. ==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 (e.g., erythromycin), certain HIV protease inhibitors (e.g., ritonavir, nelfinavir, indinavir), certain azole antifungals (e.g., ketoconazole, itraconazole, voriconazole) delavirdine, efavirenz, or a 5-HT1 receptor agonist (e.g., sumatriptan). ==Side effects==

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

Pharmacodynamics Ergotamine interacts with serotonin, adrenergic, and dopamine receptors. Ergotamine is an agonist of the serotonin 5-HT2B receptor and has been associated with cardiac valvulopathy. Despite acting as a potent serotonin 5-HT2A receptor agonist, ergotamine is said to be non-hallucinogenic similarly to lisuride. This has been posited to be due to functional selectivity at the serotonin 5-HT2A receptor. This is due to it being an avid substrate for P-glycoprotein and breast cancer resistance protein (BCRP). Only minimal amounts of the drug (~1%) cross into the brain. ==Natural occurrence==

Biosynthesis 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 pyrophosphate. 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 (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. ==Society and culture==

Legal status United States Ergotamine is a List I regulated chemical in the United States. ==See also==