Triptans and calcitonin gene-related peptide (CGRP) receptor antagonists

Abstract

While triptans, the 5-HT1B/1D agonists, are effective and generally well-tolerated in many patients up to onethird of migraine patients either may not respond well to triptans, may not tolerate their side effects, or may have contraindications that preclude their use. Recurrence, triptan-related side effects, and cardiovascular constriction effects are demerits for acute migraine treatment. CGRP receptor antagonists, the so-called gepants, were clearely designed and expected to be better than triptans. CGRP is located in sensory nerve endings around cranial blood vessels. CGRP is a strong dilator of cerebral arteries and intravenous infusion of CGRP cause a migraine attack. Olcegepant is the first selective CGRP receptor antagonist of proven efficacy in migraine. Olcegepant could only be administered intravenously and never taken beyond Phase II. Telcagepant is orally available and several completed Phase III trials have revealed positive results. In several comparative studies of telcagepant and triptans, telcegepant did not appeared more effective than zolmitriptan or rizatriptan, although it had fewer triptan-related adverse events and drug-related adverse enents. A small number of patients taking olcegepant showed marked elevation in liver transaminase levels. It was decided to discontinue development of olcegepant. New CGRP receptor antagonists would be expected for acute migraine treatment.