Document Detail


CP-96,345, a non-peptide antagonist of substance P: I. Effects on the actions mediated by substance P and related tachykinins on the guinea-pig ileum and rabbit jejunum.
MedLine Citation:
PMID:  1383834     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of a non-peptide antagonist of substance P, CP-96,345, were investigated, in vitro, on the guinea-pig ileum and the rabbit jejunum. Contractions of the guinea-pig ileum, induced by substance P and neurokinin A, were specifically inhibited by the racemate (+/-)CP-96,345 (pIC50 7.8 and 7.3, respectively). The inhibition by (+/-)CP-96,345 of contractions evoked by neurokinin B and by bradykinin (pIC50 6.1 and 4.9, respectively) was attributed to unspecific effects of the antagonist. The inhibition of substance P-induced contractions of the rabbit jejunum required a 10 times higher concentration of (+/-)CP-96,345 (pIC50 = 6.8) than was required with the guinea-pig ileum. The plateau phase of contraction of the guinea-pig ileum induced by high concentrations of substance P, neurokinin A or neurokinin B, which is known to be mediated through tachykinin receptors on intrinsic cholinergic neurones, was inhibited by 200 nM (+/-)CP-96,345 but not by the inactive enantiomer, CP-96,344. This indicates a specific inhibition of these neuronal tachykinin receptors by (+/-)CP-96,345. Contractions known to be mediated by the release of substance P, such as those evoked by capsaicin and by mesenteric nerve or field stimulation, were partially inhibited by (+/-)CP-96,345 at concentrations of 200 to 600 nM. Unspecific inhibitory effects of CP-96,345, in concentrations of 1 microM or higher, were observed on histamine-induced contractions, and on the cholinergic twitch response to electrical stimulation, of the guinea-pig ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
F J Legat; T Griesbacher; F Lembeck
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  346     ISSN:  0028-1298     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  1992 Sep 
Date Detail:
Created Date:  1992-11-19     Completed Date:  1992-11-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  315-22     Citation Subset:  IM    
Affiliation:
Institut für Experimentelle und Klinische Pharmakologie, Karl-Franzens-Universität Graz, Austria.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biphenyl Compounds / pharmacology*
Capsaicin / pharmacology
Electric Stimulation
Guinea Pigs
Hexamethonium Compounds / pharmacology
Histamine / pharmacology
Ileum / drug effects
Jejunum / drug effects
Muscle Contraction / drug effects
Muscle, Smooth / drug effects*
Parasympathetic Nervous System / drug effects
Peristalsis / drug effects
Rabbits
Stereoisomerism
Substance P / antagonists & inhibitors*,  physiology
Tachykinins / pharmacology,  physiology*
Chemical
Reg. No./Substance:
0/Biphenyl Compounds; 0/Hexamethonium Compounds; 0/Tachykinins; 132746-60-2/CP 96345; 33507-63-0/Substance P; 404-86-4/Capsaicin; 51-45-6/Histamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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