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.