Inhibitory effect of BIBN4096BS on cephalic vasodilatation induced by CGRP or transcranial electrical stimulation in the rat

Calcitonin gene‐related peptide (CGRP) is believed to play a pivotal role in the pathogenesis of migraine via activation of CGRP receptors in the trigeminovascular system. The CGRP receptor antagonist, BIBN4096BS, has proven efficacy in the acute treatment of migraine attacks and represents a new therapeutic principle. We used an improved closed cranial window model to measure changes of the middle meningeal artery (MMA) and cortical pial artery/arteriole diameter (PA) and changes in local cortical cerebral blood flow (LCBF Flux ) in anaesthetised artificially ventilated rats. The ability of BIBN4096BS (i.v.) to prevent the vasodilatatory actions of rat‐ α CGRP, β CGRP and endogenously released CGRP following transcranial electrical stimulation (TES) was investigated. BIBN4096BS was per se without vasoactive effect on any of the measured variables and significantly inhibited the hypotension induced by both types of CGRP ( P <0.001). The α CGRP induced MMA dilatation was reduced from 97.4±14 to 2.1±1.3% ( P <0.001) and the β CGRP induced dilatation was fully blocked by BIBN4096BS. ID 50 was 5.4±1.6 μ g kg −1 for α CGRP and 16.3±1.6 μ g kg −1 for β CGRP. Transcranial electrical stimulation induced a 119.1±6.9% increase in MMA diameter. BIBN4096BS (333 μ g kg −1 ) attenuated this increase (19.8±2.1%) ( P <0.001). Systemic CGRP and TES induced an increase in PA diameter that was not significantly inhibited by BIBN4096BS. The CGRP induced increase in LCBF Flux was similar not prevented by the antagonist. We suggest that systemic BIBN4096BS exerts its inhibitory action mainly on large dural blood vessels (MMA).British Journal of Pharmacology (2004) 143 , 697–704. doi: 10.1038/sj.bjp.0705966