Linked Life Data

1383835

Source:http://linkedlifedata.com/resource/pubmed/id/1383835

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1992-11-19
pubmed:abstractText
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)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
346
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
323-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
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.
pubmed:affiliation
Institut für Experimentelle und Klinische Pharmakologie, Karl-Franzens-Universität Graz, Austria.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't