Background: Migraine is a highly prevalent neurovascular disorder.
Objective: Of the many factors that have been implicated over the years, 5-hydroxytryptamine (5-HT;
serotonin) has long been involved in the pathophysiology of migraine. Certainly, some lines of evidence
suggest: (i) a 5-HT depletion from blood platelets resulting in cranial extracerebral vasodilatation;
and (ii) the effectiveness of an intravenous (i.v.) infusion of 5-HT to abort migraine in some patients.
More direct evidence comes from some drugs that influence 5-HT release and/or interact (as
agonists or antagonists) with 5-HT receptors to treat this disorder. Indeed, the development of sumatriptan
and second generation triptans in the 1990’s led to discover that these drugs produce selective
cranial extracerebral vasoconstriction (via 5-HT1B receptors) and inhibition of the trigeminovascular
system responses implicated in migraine (via 5-HT1D/5-HT1F receptors). Although the triptans represent
the current mainstay of acute antimigraine treatment, a number of patients do not respond well to
the triptans and are contraindicated in patients with cardiovascular pathologies.
Conclusion: This mini-review outlines further developments in the design of novel (non-vasoconstrictor)
antimigraine treatments acting via 5-HT receptors, including selective agonists at 5-HT1D and 5-HT1F
receptors, agonists at 5-HT1B/1D receptors combined with other properties as well as antagonists at
5-HT2B/2C, 5-HT3 and 5-HT7 receptors. It also touches upon the recent development of antagonists and
antibodies at calcitonin gene-related peptide (CGRP) and its receptors, which produce a direct blockade
of the CGRPergic vasodilator mechanisms involved in migraine. These alternative pharmacological
approaches will hopefully lead to less side-effects.