Oral CGRP receptor antagonists (gepants) in migraine therapy

Abstract

Migraine therapy is classified into two categories : attack–aborting and prophylactic treatments. Triptans are very efficacious in alleviating migraine attacks. Nevertheless, the vasoconstrictive properties of triptans restrict their clinical utility. Because simple analgesics and NSAIDs are suboptimal for the acute therapy of migraine, there have been demands for alternative non–vasoconstrictive drugs. Calcitonin gene–related peptide (CGRP) is known to play a pivotal role in the pathogenesis of migraine. Migraine–like attacks are induced in a delayed manner by CGRP administration exclusively in migraine sufferers. BIBN 4096 BS, a first CGRP receptor antagonist, was shown to be effective in ameliorating migraine attacks in a dose–dependent manner, thus demonstrating that CGRP was a bona fide therapeutic target of migraine. It was also revealed that CGRP receptor blockade did not entail any significant cardiovascular risk. There has been much progress in the development of CGRP receptor antagonist in the last decade. Consequently, three CGRP receptor antagonists (gepants) have been approved and marketed globally.