Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy

Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide‐ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5‐HT 1B and 5‐HT 1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain‐producing intracranial extracerebral blood vessels at the 5‐HT 1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5‐HT 1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long‐term experience.