Effects of the CGRP receptor antagonist BIBN4096BS on capsaicin‐induced carotid haemodynamic changes in anaesthetised pigs

• Published in: British journal of pharmacology Vol. 140; no. 2; pp. 329 - 338
• Main Authors: Kapoor, Kapil, Arulmani, Udayasankar, Heiligers, Jan P C, Garrelds, Ingrid M, Willems, Edwin W, Doods, Henri, Villalón, Carlos M, Saxena, Pramod R
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2003; Nature Publishing
• Subjects: Anesthesia; Animals; Arteriovenous anastomoses; BIBN4096BS; Biological and medical sciences; Blood Flow Velocity - drug effects; Blood Pressure - drug effects; Calcitonin Gene-Related Peptide - blood; capsaicin; Capsaicin - pharmacology; Carotid Arteries - drug effects; Carotid Arteries - physiology; carotid circulation; CGRP; CGRP receptor antagonists; Dose-Response Relationship, Drug; Female; Heart Rate - drug effects; Hemodynamics - drug effects; Jugular Veins - drug effects; Jugular Veins - metabolism; Medical sciences; microspheres; migraine and pig; Oxygen - blood; Pharmacology. Drug treatments; Receptors, Calcitonin Gene-Related Peptide - antagonists & inhibitors; Swine; Capsaicin; migraine and pig; Cardiovascular disease; CGRP receptor antagonists; Neuropeptide; Vascular disease; Pain; Antagonist; CGRP receptor; BIBN4096BS; Cerebrovascular disease; Ungulata; Nervous system diseases; Microsphere; Arteriovenous anastomoses; microspheres; Migraine; Calcitonin gene related peptide; Cerebral disorder; Pig; Vertebrata; Mammalia; Animal; Central nervous system disease; Artiodactyla; Hemodynamics; CGRP; carotid circulation
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705451

Calcitonin gene‐related peptide (CGRP), a potent vasodilator released from capsaicin‐sensitive trigeminal sensory nerves, seems to be involved in the pathogenesis of migraine. Hence, CGRP receptor antagonists may serve as a novel treatment for migraine. This study was therefore designed to investigate the effects of BIBN4096BS (100, 300 and 1000 μg kg−1, i.v.), a potent and selective CGRP receptor antagonist, on capsaicin‐induced carotid haemodynamic changes in anaesthetised pigs. Both vagosympathetic trunks were cut and phenylephrine was infused into the carotid artery (i.c.) to support carotid vascular tone.
Infusions of capsaicin (0.3, 1, 3 and 10 μg kg−1 min−1, i.c.) did not alter the heart rate, but dose‐dependently increased the mean arterial blood pressure. This moderate hypertensive effect was not modified by BIBN4096BS.
Capsaicin infusion (10 μg kg−1 min−1, i.c.) increased total carotid, arteriovenous anastomotic and tissue blood flows and conductances as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. These responses to capsaicin were dose‐dependently blocked by BIBN4096BS.
Capsaicin infusion (10 μg kg−1 min−1, i.c.) more than doubled the jugular venous plasma concentration of CGRP. This effect was not blocked, but rather increased, by BIBN4096BS.
The above results show that BIBN4096BS behaves as a potent antagonist of capsaicin‐induced carotid haemodynamic changes that are mediated via the release of CGRP. Therefore, this compound may prove effective in the treatment of migraine.
British Journal of Pharmacology (2003) 140, 329–338. doi:10.1038/sj.bjp.0705451