Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells

Several lines of evidence suggest that a calcitonin-gene related peptide (CGRP) receptor antagonist may serve as a novel abortive migraine treatment Here we present data on a human cell line and isolated human vessels for such an antagonist, BIBN4096BS. On SK-N-MC membranes, radiolabelled CGRP was displaced by both CGRP-(8-37) and BIBN4096BS, yielding pK(i) values of 8.5 and 11.4, respectively. Functional studies with SK-N-MC cells demonstrated that CGRP-induced cAMP production was antagonised by both CGRP(8-37) and BIBN4096BS with pA(2) values of 7.8 and 11.2, respectively. Isolated human cerebral, coronary and omental arteries were studied with a sensitive myograph technique. CGRP induced a concentration-dependent relaxation that was antagonized by both CGR-P-(8-37) and BIBN4096BS in a competitive manner. CGRP was a weaker agonist on coronary arteries as compared to intracranial arteries; however, BIBN4096BS was an equally effective antagonist. In human omental arteries, CGRP did not induce relaxation. BIBN4096 had a pA(2) value of 10.1 in cerebral and 10.4 in coronary arteries. The results of clinical trials with BIBN4096BS for acute migraine attacks are awaited with great interest. (C) 2002 Elsevier Science B.V. All rights reserved.