CGRP antagonists: hope for a new era in acute migraine treatment.

Calcitonin gene-related peptide (CGRP) has a widespread distribution throughout the trigeminovascular system and other brain areas involved in migraine pathogenesis. Serum levels of CGRP are elevated during the migraine attack and return to normal with alleviation of pain. Intravenous injection of CGRP in migraineurs results in delayed headache similar to migraine. Since CGRP receptor antagonists lack direct vasoconstrictor activity, this therapeutic approach may offer advantages over the current mainstay of specific acute migraine treatment with 5-HT1B/1D receptor agonists (triptans), contra-indicated in patients with underlying cardiovascular disease. Intravenous BIBN4096BS (olcegepant) and oral MK-0974 (telcagepant), two CGRP-receptor antagonists, were safe and effective in the treatment of migraine attacks in Phase I and II trials. In a Phase III clinical trial, the efficacy of telcagepant 300 mg was comparable to that of zolmitriptan 5 mg. We intend to review the rationale for the use of CGRP-receptor antagonists, and to outline current developments and future perspectives.