, Volume 10, Issue 4, pp 271-286
Date: 30 Aug 2012

Serotonin 5-HT1B/1D Receptor Agonists in Migraine

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Abstract

The development and clinical use of the serotonin 5-HT1 receptor agonists, collectively known as the ‘triptans’, has ushered in a new age for clinicians treating patients with migraine, as well as a new era for those who respond to the medicines. The triptans that are currently in use (sumatriptan, naratriptan, rizatriptan and zolmitriptan) and those in development [almotriptan, eletriptan and frovatriptan (SB-209509, VML-251)] all share a common pharmacology of 5-HT1B/1D receptor agonist activity.

Administration of a triptan during an acute migraine is aimed, via an interruption of the pathophysiology of this disorder, at rapid and well tolerated relief of headache and associated symptoms of migraine. Migraine probably involves a combination of cranial vasodilatation, with peripheral trigeminal nerve activation and consequent excitation of trigeminal neurons within the caudal brainstem and upper cervical spinal cord (the trigeminocervical complex). Triptans may act by constricting cranial vessels through 5-HT1B receptors, by inhibiting peripheral trigeminal nerve afferents that innervate the vessels and pain-producing dura mater through 5-HT1D receptors, or by inhibiting central trigeminal neuronal traffic through 5-HT1D receptors, or by a combination of these mechanisms. Peripheral neuronal inhibition is likely to involve inhibition of calcitonin generelated peptide (CGRP) release and perhaps to some degree inhibition of a trigeminally driven inflammatory process.

Some aspects of the pharmacokinetics of the various triptans, such as the relationship between time to reach peak plasma concentrations and half-lives and clinical efficacy, may reveal information about the fundamental processes at work in acute migraine. The triptans have been a source of considerable interest because they have provided important clues to the basic pathophysiology of migraine and point to an important role for the CNS in this disorder.