Calcitonin gene-related peptide (CGRP) is linked to migraine and other primary 
headache disorders. It is found in every location described in migraine genesis 
and processing, including meninges, trigeminal ganglion, trigeminocervical 
complex, brainstem nuclei, and cortex. It is released in animal models following 
stimulation of the CNS similar to that seen in migraine, and triptans inhibit 
this release. Injection of CGRP into migraineurs results in delayed headache 
similar to migraine. Elevation of CGRP occurs during migraine, resolving 
following migraine-specific treatment. Finally, and most importantly, CGRP 
receptor antagonists terminate migraine with efficacy similar to triptans. Both 
intravenous olcegepant (BIBN 4096 BS) and oral telcagepant (MK-0974) have been 
effective, safe, and well tolerated in phase I and II studies. Telcagepant is 
currently in phase III trials, and preliminary results are favorable. The 
potential for a migraine-specific medication without vasoconstrictive or 
vascular side effects is enormous. CGRP receptor blockade may also have 
applications in other pathologic and pain syndromes.