Olcegepant: Antimigraine drug CGRP antagonist

Migraine involves dysfunction of brainstem pathways that normally modulate sensory input. The involvement of calcitonin gene-related peptide (CGRP) in migraine pathology is supported by both clinical and experimental evidence. The release of CGRP and other neuropeptides from trigeminal nerves is thought to mediate neurogenic inflammation within the meninges, which contributes to the generation of severe cerebral pain experienced during migraine attacks. Hence, structure-activity relationship studies have been conducted in an attempt to develop small molecules that behave as CGRP antagonists. Recently, the development of a potent, nonpeptide CGRP antagonist, BIBN-4096BS (olcegepant), represented a major breakthrough. BIBN-4096BS demonstrates very high affinity for the human CGRP receptor expressed in SK-N-MC cells and may be useful in the treatment of migraine, as well as providing new information on CGRP receptor subtypes. Copyright