The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS reduces neurogenic increases in dural blood flow

Abstract

In an in vivo preparation of the exposed rat cranial dura mater electrical field stimulation causes increases in blood flow that are mainly due to the vasodilatory effect of calcitonin gene-related peptide (CGRP) released from meningeal afferents. In this preparation the effect of BIBN4096BS, a non-peptide competitive antagonist of CGRP receptors, was examined. Additionally, in an in vitro preparation of the hemisected rat skull the effect of BIBN4096BS on CGRP release stimulated by activation of meningeal afferents was analysed. Injection of BIBN4096BS at cumulative doses of 300 μg/kg and 900 μg/kg caused dose-dependent inhibition of the electrically evoked blood flow increases. The basal blood flow and vital parameters were not significantly changed by any dose. In the hemisected skull BIBN4096BS at 10 − 6 M did not alter the CGRP release evoked by depolarizing K + concentrations or antidromic electrical stimulation of the trigeminal ganglion. We conclude that neurogenic increases in dural blood flow are reduced by BIBN4096BS without changing basal vascular parameters. This peripheral effect may be important with regard to CGRP receptor inhibition as an antimigraine strategy.