Pharmacological profile of BIBN4096BS, the first selective small molecule CGRP antagonist

Calcitonin gene-related peptide (CGRP) is one of the most patent endogenous vasodilators known. This peptide is increased during migraine attacks and has been implicated in the pathogenesis of migraine headache. Here we repor t on the first small molecule selective CGRP antagonist: BIBN4096BS. In vit ro, this compound is extremely potent at primate CGRP receptors exhibiting an affinity (K-i) for human CGRP receptors of 14.1 +/- 6.3 (n = 4) phl. In an in vitro model, BIBN4096BS in doses between 1 and 30 mu g kg(-1) (i.v.) inhibited the effects of CGRP, released by stimulation of the trigeminal ga nglion, on facial blood flow in marmoset monkeys. It is concluded that BIBN 4096BS is a potent and selective CGRP antagonist.