Document Detail

CP-96,345, a non-peptide antagonist of substance P: II. Actions on substance P-induced hypotension and bronchoconstriction, and on depressor reflexes in mammals.
MedLine Citation:
PMID:  1383835     Owner:  NLM     Status:  MEDLINE    
In order to extend the in vivo pharmacological profile of CP-96,345 ((2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)- methyl)-1-azabicyclo[2.2.2]octan-3-amine dihydrochloride), a non-peptide antagonist of substance P, the compound was tested against substance P-induced effects on blood pressure in rabbits and on respiration pressure in guinea-pigs. In addition, CP-96,345, and its inactive (2R,3R)-enantiomer, CP-96,344, were also tested in 2 models involving presumably substance P-mediated reflexes in the rat. The fall in blood pressure evoked by i.v. injections of substance P in the rabbit was inhibited by 0.3 mumol kg-1 CP-96,345 i.v. for at least 30 min, and almost abolished, for at least 2 h, by 3 mumol kg-1. In guinea-pigs, the bronchoconstriction induced by i.v. injections of substance P, but not that in response to histamine or bradykinin, was inhibited by CP-96,345 (0.6 and 6.0 mumol kg-1, i.v.) in a dose-dependent manner and this inhibition lasted for 40 min and 70 min, respectively. CP-96,345 (3-20 mumol kg-1, i.v.) reduced depressor reflexes in response to stimulation of peripheral capsaicin-sensitive neurones in the rat. However, the inhibition was not dose-dependent and was also seen with the inactive enantiomer, CP-96,344. This effect can hardly be attributed to receptor-specific effects of CP-96,345 and may be related to unspecific actions such as those involved in the cardiac depression exhibited by both enantiomers. The present results show that CP-96,345 is a potent antagonist of substance P in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
T Griesbacher; J Donnerer; F J Legat; 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:  323-7     Citation Subset:  IM    
Institut für Experimentelle und Klinische Pharmakologie, Karl-Franzens-Universität Graz, Austria.
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MeSH Terms
Biphenyl Compounds / pharmacology*
Blood Pressure / drug effects*
Bronchoconstriction / drug effects*
Guinea Pigs
Rats, Sprague-Dawley
Reflex / drug effects*
Substance P / antagonists & inhibitors*,  metabolism,  pharmacology
Tachykinins / antagonists & inhibitors
Reg. No./Substance:
0/Biphenyl Compounds; 0/Tachykinins; 132746-60-2/CP 96345; 33507-63-0/Substance P

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

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