CGRP antagonists in treatment of migraine attacks

Triptans are the drugs of choice in moderate to severe migraine attacks. It is estimated that they are ineffective in one-third of patients. Furthermore, triptans are contraindicated in patients with cardiovascular diseases. Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide. It has been suggested that it plays a critical role in migraine pathophysiology. Increased CGRP levels have been reported during migraine and cluster headache attacks. Furthermore, it was shown that intravenous CGRP induces migraine-like headaches in susceptible individuals. Triptans decrease elevated CGRP level back to normal. Based on these findings, it was proposed that blockage of CGRP receptors may be effective in aborting a migraine attack. Olcegepant was the first CGRP antagonist investigated in patients with migraine. Despite confirmed efficacy, its development was discontinued due to the difficulties in producing an orally available formulation. Telcagepant was the first CGRP antagonist available in tablets. Despite promising clinical data, the clinical development program for the drug was discontinued due to concerns about liver toxicity. This year, the results of phase III trial on ubrogepant, a new CGRP antagonists, were published. Its efficacy is comparable to that of triptans, and its adverse event profile is similar to that of placebo. No serious adverse reactions were reported in patients treated with this drug. Since CGRP antagonists do not show vasoconstrictive proprieties, they may be used in patients with cardiovascular diseases, in whom triptans are contraindicated. The studies on the efficacy and tolerability of CGRP antagonists are promising, and it is hoped that they will expand the possibilities of effective abortive treatment of migraine.