Gepants

Gepants are a class of small-molecule antagonists of the calcitonin gene-related peptide (CGRP) receptor. By blocking CGRP from binding to its receptor, gepants aim to inhibit a signaling pathway implicated in migraine pathophysiology. They are used for both acute treatment of migraine attacks and, for some agents, preventive therapy.

Representative gepants include ubrogepant and rimegepant, approved for acute treatment, and atogepant, approved for prevention. A newer gepant, zavegepant, has been developed as a nasal spray for acute treatment. Atogepant is taken on a daily basis for migraine prevention, whereas ubrogepant and rimegepant are taken as needed during attacks.

Gepants are non-vasoconstrictive, offering an alternative to triptans for patients with cardiovascular risk or who do not tolerate triptans. Their pharmacology centers on antagonism of the CGRP receptor, which reduces the neurogenic inflammation and vasodilatory signaling associated with migraine.

Common adverse events are generally mild and may include nausea, dry mouth, and dizziness. Hepatic safety concerns have been noted with some gepants, particularly with long-term use or in patients with liver impairment, and monitoring may be advised. Drug interactions are possible, as many gepants are metabolized by hepatic enzymes such as CYP3A4.

Overall, gepants provide targeted CGRP-receptor antagonism with a distinct safety and administration profile compared with traditional migraine therapies, expanding options for both acute and preventive management.