Development of CGRP antagonists for the treatment of migraine.

Migraine is one of the most common neurological disorders, involving periodical attacks of headache and nausea as well as a plethora of other symptoms. Although considerable progress has been made, the pathophysiology of migraine is still not understood. However, several observations point to an involvement of calcitonin gene-related peptide (CGRP). Migraine headache involves the activation of the trigeminal system and dilatation of cranial vessels. CGRP is localized to neurons in the trigeminal ganglia and CGRP levels are increased during a migraine attack, presumably causing the vasodilation observed. Accordingly, it is conceivable that inhibition of CGRP-evoked dilatation of the cranial vessels may provide a novel treatment for migraine headache. The non-peptidic CGRP antagonist BIBN-4096BS (Boehringer Ingelheim) is presently under clinical investigation to assess the importance of CGRP in migraine headache and to answer the question of whether the concept of CGRP antagonists may offer advantages, e.g., higher efficacy, lower recurrence rate or improved side-effect profile, compared to the currently used antimigraine drugs.