The 5-HT_1B and 5-HT_1D agonists in acute migraine therapy: Ergotamine, dihydroergotamine, and the triptans

The advent of the triptans revolutionized acute migraine treatment. The older migraine-specific drugs, the ergot alkaloids (ergotamine and dihydroergotamine), also relieve migraine attacks through agonism at the 5-HT_1B and 5-HT_1D receptors, but the triptans have much greater specificity for these receptors. Unlike the ergot alkaloids, the triptans do not activate many other receptor types, and therefore are much better tolerated. This reduction in side effects greatly enhanced their clinical utility as it allowed a far greater proportion of patients to take a full therapeutic dose. As a result, the clinical use of ergotamine is minimal today, although dihydroergotamine still has a significant clinical role. There is extensive evidence that the seven triptans available today, sumatriptan, zolmitriptan, rizatriptan, eletriptan, naratriptan, almotriptan, and frovatriptan, are effective in the acute treatment of migraine. Available formulations include oral tablets, orally dissolving tablets, subcutaneous injections, nasal sprays, and in some countries, rectal suppositories. For optimal benefit, therapy needs to be individualized for a given patient both regarding the triptan chosen and the formulation. This chapter discusses the ergot alkaloids and the triptans, including mechanism of action, evidence for efficacy, clinical use, and adverse effects.