Serotonin 5-HT1B/1D receptor agonists in migraine -: Comparative pharmacology and its therapeutic implications

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 gene-related peptide (CGRP) release and perhaps to some degree inhibition of a trigeminally driven inflammatory process.