The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments

Title:The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments

Volume: 17 Issue: 11

Author(s): Carlos M. Villalón*Antoinette Maassen VanDenBrink

Affiliation:

• Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F,Mexico

Keywords: Antimigraine drugs, drug development, migraine, neurovascular disorder, triptans, 5-HT receptors.

Abstract: 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-HT_1D/5-HT_1F 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-HT_1D and 5-HT_1F receptors, agonists at 5-HT_1B/1D receptors combined with other properties as well as antagonists at 5-HT_2B/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.

Cite this article as:

Villalón M. Carlos*, VanDenBrink Maassen Antoinette, The Role of 5-Hydroxytryptamine in the Pathophysiology of Migraine and its Relevance to the Design of Novel Treatments, Mini-Reviews in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1389557516666160728121050