Activation of 5-hydroxytryptamine_1B/1D/1F receptors as a mechanism of action of antimigraine drugs

Abstract

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 α-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT_1B/1D receptor agonists, showing fewer side effects due to their receptor specificity. In the last years, compounds that bind specifically to 5-HT_1D, 5-HT_1F and 5-HT₇ receptors have been explored for their antimigraine potential. Furthermore, the serotonergic system seems to act in tight connection with the glutamatergic as well as the CGRP-ergic systems, which may open novel therapeutic avenues.

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-HT_1F 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.

Keywords::

• 5-HT
• 5-HT receptor
• antimigraine drugs
• migraine
• sumatriptan
• triptan

Acknowledgement

M B Ramírez Rosas and S Labruijere contributed equally to this work.

Notes

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