Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells.

Abstract

Several lines of evidence suggest that a calcitonin-gene related peptide (CGRP) receptor antagonist may serve as a novel abortive migraine treatment. Here we present data on a human cell line and isolated human vessels for such an antagonist, BIBN4096BS. On SK-N-MC membranes, radiolabelled CGRP was displaced by both CGRP-(8-37) and BIBN4096BS, yielding pK(i) values of 8.5 and 11.4, respectively. Functional studies with SK-N-MC cells demonstrated that CGRP-induced cAMP production was antagonised by both CGRP-(8-37) and BIBN4096BS with pA(2) values of 7.8 and 11.2, respectively. Isolated human cerebral, coronary, and omental arteries were studied with a sensitive myograph technique. CGRP induced a concentration-dependent relaxation that was antagonized by both CGRP-(8-37) and BIBN4096BS in a competitive manner. CGRP was a weaker agonist on coronary arteries as compared to intracranial arteries; however, BIBN4096BS was an equally effective antagonist. In human omental arteries, CGRP did not induce relaxation. BIBN4096 had a pA(2) value of 10.1 in cerebral and 10.4 in coronary arteries. The results of clinical trials with BIBN4096BS for acute migraine attacks are awaited with great interest.

• Authors: Lars Edvinsson, Rikard Alm, Duncan Shaw, Ruth Z Rutledge, Kenneth S Koblan, Jenny Longmore, Stefanie A Kane
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 434 Issue 1-2 Pg. 49-53 (Jan 02 2002) ISSN: 0014-2999 [Print] Netherlands
• PMID: 11755165 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcitonin Gene-Related Peptide Receptor Antagonists
• Piperazines
• Quinazolines
• Cyclic AMP
• Calcitonin Gene-Related Peptide
• olcegepant

Topics

• Calcitonin Gene-Related Peptide (metabolism)
• Calcitonin Gene-Related Peptide Receptor Antagonists
• Cerebral Arteries (drug effects, physiology)
• Coronary Vessels (drug effects, physiology)
• Cyclic AMP (biosynthesis)
• Humans
• In Vitro Techniques
• Omentum (blood supply)
• Piperazines (pharmacology)
• Quinazolines (pharmacology)
• Vasodilation (drug effects)