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Clinical and Preclinical Rationale for CGRP‐Receptor Antagonists in the Treatment of Migraine
Author(s) -
Tepper Stewart J.,
Stillman Mark J.
Publication year - 2008
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2008.01214.x
Subject(s) - migraine , triptans , calcitonin gene related peptide , medicine , cortical spreading depression , sumatriptan , trigeminal ganglion , anesthesia , migraine treatment , pharmacology , neuroscience , receptor , neuropeptide , agonist , psychology , sensory system
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.