Proinflammatory mediators and migraine pathogenesis: Moving towards CGRP as a target for a novel therapeutic class

Migraine is a complex neurological disorder in which genetic and environmental factors interact. At present, frontline therapies in migraine's acute treatment include the use of NSAIDS and triptans. Restrictions in the use of frontline drugs for migraine treatment and evidence concerning CGRP's key role led research towards new pathways involved in migraine pathophysiology. CGRP is a strong vasodilatory neuropeptide released from activated trigeminal sensory nerves. The development of CGRP antagonists has also been driven by the fact that triptans are vasoconstrictive and cannot be used in patients with vascular risk factors. BIBN4096 (olcegepant) is the first CGRP antagonist for the treatment of migraine which has been tested in clinical trials, but its principal limitation is that BIBN4096 presents low oral bioavailability and has only been tested through intravenous formulation. The first oral nonpeptide CGRP antagonist, MK-0974 (telcagepant), has recently been shown to be highly effective in the treatment of migraine attacks. This development can be considered the most important pharmacological breakthrough for migraine treatment since the introduction of sumatriptan in the early 1990s. These results are important since they confirm the current pathophysiological concept of migraine. The future introduction of CGRP antagonists in clinical practice could represent a progress for migraine therapy. © 2008 Expert Reviews Ltd.