The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS reduces neurogenic increases in dural blood flow.
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 microg/kg and 900 microg/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.
Tröltzsch
Markus
M
Institute of Physiology & Pathophysiology, University of Erlangen-Nürnberg, Universitätsstr. 17, D-91054 Erlangen, Germany.
Denekas
Thomas
T
Messlinger
Karl
K
D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004388:Dura Mater / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology; D012886:Skull / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000502:physiology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant