The best magazine
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.
The concept that a calcitonin gene-related peptide (CGRP)-receptor antagonist would be of clinical utility in migraine goes back to the late 1980s. Relief of migraine corresponds to reduction of blood CGRP, and migraine pharmacotherapies decrease CGRP. A CGRP-receptor antagonist could block vasodilation and avoid vasoconstriction in the meninges, as well as alter CGRP action in the trigeminal ganglion and reduce pain transmission. Two CGRP-receptor antagonists, olcegepant (BIBN 4096 BS) and telcagepant (MK-0974), have been tested in phase II trials in humans and showed clinical benefit and excellent tolerability, with recent presentation of phase III data on telcagepant suggesting that proof of concept is positive.
Source: ...