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

Edvinsson, Lars LU ; Alm, Rikard; Shaw, Duncan; Rutledge, Ruth Z; Koblan, Kenneth S; Longmore, Jenny and Kane, Stefanie A (2002) In European Journal of Pharmacology 434(1-2). p.49-53
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... (More)
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. (Less)
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keywords
Support Non-U.S. Gov't, Receptors Calcitonin Gene-Related Peptide : antagonists & inhibitors, Quinazolines : pharmacology, Piperazines : pharmacology, Omentum : blood supply, In Vitro, Human, Cyclic AMP : biosynthesis, Coronary Vessels : drug effects : physiology, Calcitonin Gene-Related Peptide : metabolism, Cerebral Arteries : drug effects : physiology, Vasodilation drug effects
in
European Journal of Pharmacology
volume
434
issue
1-2
pages
49 - 53
publisher
Elsevier
external identifiers
  • wos:000173119400008
  • pmid:11755165
  • scopus:0037005741
ISSN
1879-0712
DOI
10.1016/S0014-2999(01)01532-1
language
English
LU publication?
yes
id
32279e70-e767-40e8-806c-7e5faa9026ae (old id 106924)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11755165&dopt=Abstract
date added to LUP
2007-06-28 16:20:26
date last changed
2017-10-22 03:42:26
@article{32279e70-e767-40e8-806c-7e5faa9026ae,
  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.},
  author       = {Edvinsson, Lars and Alm, Rikard and Shaw, Duncan and Rutledge, Ruth Z and Koblan, Kenneth S and Longmore, Jenny and Kane, Stefanie A},
  issn         = {1879-0712},
  keyword      = {Support Non-U.S. Gov't,Receptors Calcitonin Gene-Related Peptide : antagonists & inhibitors,Quinazolines : pharmacology,Piperazines : pharmacology,Omentum : blood supply,In Vitro,Human,Cyclic AMP : biosynthesis,Coronary Vessels : drug effects : physiology,Calcitonin Gene-Related Peptide : metabolism,Cerebral Arteries : drug effects : physiology,Vasodilation drug effects},
  language     = {eng},
  number       = {1-2},
  pages        = {49--53},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells.},
  url          = {http://dx.doi.org/10.1016/S0014-2999(01)01532-1},
  volume       = {434},
  year         = {2002},
}