Conflict of Interest: Dr. Tepper has received grants and research support from Allergan, Alexza, ANS/Advanced Bionics, AstraZeneca, Eisai, Endo, Forrest, GSK, King, MAP, Merck, Medtronix, Minster, Neurochem, NMT, Novartis, Nupathe, OrthoMcNeil, Pfizer, Pozen, Proethic, Takeda, Winston, and Vernalis; has been a consultant for Allergan, AstraZeneca, Coherex, Elan, Endo, Forrest, GSK, Merck, NMT, OrthoMcNeil, and Vernalis; has been on the speakers bureau of Allergan, AstraZeneca, Endo, GSK, Merck, NMT, OrthoMcNeil, Pfizer, and Valeant; and is on the advisory boards of GSK and Merck. Dr. Stillman has received grants and research support from GSK and MAP; is on the speakers bureau of Allergan, GSK, Merck, OrthoMcNeil, Pfizer, and Valeant; and is on the advisory boards of GSK and Pfizer.
Clinical and Preclinical Rationale for CGRP-Receptor Antagonists in the Treatment of Migraine
Article first published online: 2 SEP 2008
© 2008 the Authors. Journal compilation © 2008 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 48, Issue 8, pages 1259–1268, September 2008
How to Cite
Tepper, S. J. and Stillman, M. J. (2008), Clinical and Preclinical Rationale for CGRP-Receptor Antagonists in the Treatment of Migraine. Headache: The Journal of Head and Face Pain, 48: 1259–1268. doi: 10.1111/j.1526-4610.2008.01214.x
- Issue published online: 2 SEP 2008
- Article first published online: 2 SEP 2008
- Accepted for publication June 16, 2008.
- calcitonin-gene related peptide;
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.