Activation of 5-hydroxytryptamine(1B/1D/1F) receptors as a mechanism of action of antimigraine drugs

Introduction: The introduction of the triptans (5-hydroxytryptamine (5-HT)(1B/1D) receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine. Areas covered: In this review the different types of antimigraine drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific antimigraine drugs were the ergot alkaloids, consisting of ergotamine, dihydroergotamine and methysergide, which are agonists at 5-HT receptors, but can also bind alpha-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT1B/1D receptor agonists, showing fewer side effects due t Expert opinion: Although the triptans are very effective in treating migraine attacks, their shortcomings have stimulated the search for novel drugs. Currently, the focus is on 5-HT1F receptor agonists, which seem devoid of vascular side effects. Moreover, novel compounds that affect multiple transmitter and/or neuropeptide systems that are involved in migraine could be of therapeutic relevance.