BIBN4096BS is a potent competitive antagonist of the relaxant effects of α-CGRP on human temporal artery:: comparison with CGRP(8-37)

1 Release of CGRP during migraine may produce harmful dilatation of cranial arteries, thereby possibly causing pain. We have compared the antagonism by BIBN4096BS and CGRP(8-37) of the relaxant effects of alpha-CGRP on rings of human temporal artery. 2 alpha-CGRP relaxed the arteries precontracted with 9-24 mM KCl (-logEC(50) = 9.4) nearly as efficaciously as sodium nitroprusside (10 mum). 3 BIBN4096BS (0.1 - 100 nM) antagonized the effects of alpha-CGRP in surmountable manner with slopes of Schild-plots not different from unity. -LogK(B) values of 10.1 and 10.4 were estimated for BIBN4096BS when administered before or during the KCl-contracture respectively. 4 BIBN4096BS (1 muM) did not modify the relaxant effects of papaverine and sodium nitroprusside. 5 CGRP(8-37) (1 - 10 muM) antagonized the effects of alpha-CGRP in a surmountable manner with slopes of Schild-plots not different from unity. -LogK(B) values of 6.6 and 6.7 were estimated for CGRP(8-37) administered before or during the KCl-contracture respectively. 6 The high affinity of BIBN4096BS for CGRP receptors of human temporal artery makes it an excellent tool to explore the hypothesis of CGRP-evoked cerebral vasodilation in migraine.