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.