Document Detail

Effect of two novel CGRP-binding compounds in a closed cranial window rat model.
MedLine Citation:
PMID:  17477918     Owner:  NLM     Status:  MEDLINE    
We investigated the in vivo effects of two novel calcitonin gene-related peptide (CGRP) binding molecules in the genuine closed cranial window model in the rat. The RNA-Spiegelmer (NOX-C89) and the monoclonal CGRP antibody are CGRP scavengers and might be used as an alternative to CGRP-receptor antagonists in the treatment of migraine. Rats were anaesthetized and a closed cranial window established. Changes in dural and pial artery diameter and mean arterial blood pressure were measured simultaneously. Infusion of the RNA-Spiegelmer or the CGRP antibody alone had no effect on the arteries or the mean arterial blood pressure. We then used a bolus of 0.3 microg/kg CGRP (n=6) or electrical stimulation (25 V, 5 Hz, 1 ms pulse width and of 10 s of duration) (n=6) to induce dilatation of dural and pial arteries (mediated via CGRP-receptors). Pre-treatment with the RNA-Spiegelmer inhibited CGRP-induced vasodilatation of the dural artery (from 38+/-17% to 7+/-3%) and the pial artery (from 14+/-1% to 3+/-2%) (P<0.05). The RNA-Spiegelmer, however, did not significantly inhibit dilatation induced by electrical stimulation (P>0.05). The CGRP antibody caused a significant reduction of the dural artery diameter caused by intravenous CGRP-infusion (from 23+/-5% to 12+/-3%) (P<0.05), but did not inhibit dilatation caused by electrical stimulation (P>0.05). In conclusion, the CGRP scavengers effectively inhibited the effect of circulating CGRP but do not modify the effect of electrical stimulation and the consequent liberation of CGRP from perivascular sensory nerve fibres.
Louise Juhl; Lars Edvinsson; Jes Olesen; Inger Jansen-Olesen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-14
Journal Detail:
Title:  European journal of pharmacology     Volume:  567     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-05-28     Completed Date:  2007-07-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  117-24     Citation Subset:  IM    
Department of Neurology, Glostrup Research Institute, Glostrup Hospital, University of Copenhagen, DK-2600, Glostrup, Denmark.
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MeSH Terms
Antibodies, Monoclonal / pharmacology*
Aptamers, Nucleotide / pharmacology*
Blood Pressure / drug effects
Calcitonin Gene-Related Peptide / immunology,  metabolism*,  pharmacology
Disease Models, Animal
Dura Mater / blood supply
Electric Stimulation
Meningeal Arteries / drug effects,  physiopathology
Middle Cerebral Artery / drug effects,  physiopathology
Migraine Disorders / drug therapy
Oligonucleotides / pharmacology*
Pia Mater / blood supply
Polyethylene Glycols / chemistry
Protein Binding
Rats, Sprague-Dawley
Vasodilation / drug effects
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Aptamers, Nucleotide; 0/NOX-C29; 0/Oligonucleotides; 0/Polyethylene Glycols; 83652-28-2/Calcitonin Gene-Related Peptide

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