Gepants, calcitonin gene-related peptide antagonists, for abortive treatment of migraine: current status

Abstract

Migraine is a neurovascular disorder characterized by unilateral, recurrent, pulsating, throbbing, and moderate to severe headache. Triptans use is often limited by their poor efficacy, reports of poor responders, and contraindicated in patients with cardiovascular disorders. Calcitonin gene-related peptide (CGRP), a neuropeptide, regulates vascular tonicity as well as potent pain mediator, and both the mechanisms involved in development of migraine headache. Gepants are non-peptide, small molecules, highly selective, and potent CGRP antagonists. These novel drugs have been approved for abortive treatment of acute migraine with or without aura. These are being evaluated for their effectiveness and showing promising results in the prevention of migraine. Gepants do not have vasoconstrictive properties, are safe to use in patients with cardiovascular risk, and best alternative to triptan therapy. These are available in tablet, orally disintegrating tablet, and nasal forms to improve patient compliance. Ubrogepant and rimegepant are the two oral CGRP antagonists approved whereas atogepant and zavegepant are at late stage of development for approval.