Document Detail


CP-96,345, a non-peptide antagonist of substance P. III. Cardiovascular effects in mammals unrelated to actions on substance P receptors.
MedLine Citation:
PMID:  1383836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cardiovascular effects of CP-96,345, a non-peptide antagonist of substance P, were analyzed in vivo and in vitro. In the anaesthetized rat, the i.v. injection of 3 mumol kg-1 of CP-96,345 induced a fall in mean arterial blood pressure and a reduction in heart rate. Similar effects were obtained with the enantiomer CP-96,344 (2R,3R)-cis-isomer of CP-96,345) which does not interact with substance P receptors. Both enantiomers, at a concentration of 10 microM, decreased the beating frequency of the isolated atria and of the isolated perfused heart of the guinea-pig to a similar extent, and caused transient coronary dilatation. CP-96,345 (10 microM) decreased the spontaneous sinus rate, prolonged the atrioventricular-nodal conduction interval and the His-bundle conduction interval of the perfused guinea-pig heart. The intraventricular spread of conduction was markedly inhibited. During programmed stimulation 10 min after the beginning of the drug application, the effective refractory periods evaluated by stimulation with premature beats, as well as rate dependent effective refractory periods, of the atrioventricular node, of the atrial and of the ventricular myocardium, were prolonged. Sinus node recovery time was also prolonged. It was concluded that these cardiac effects of CP-96,345 were not caused by an action of the compound on substance P receptors.
Authors:
J Donnerer; U Stark; H A Tritthart; 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:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  328-32     Citation Subset:  IM    
Affiliation:
Institut für Experimentelle und Klinische Pharmakologie, Universität Graz, Austria.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Animals
Biphenyl Compounds / pharmacology*
Blood Pressure / drug effects
Decerebrate State / physiopathology
Electrocardiography
Electrophysiology
Guinea Pigs
Heart / drug effects
Heart Rate / drug effects
Hemodynamics / drug effects*
Rats
Rats, Sprague-Dawley
Receptors, Neurokinin-1
Receptors, Neurotransmitter / drug effects*
Substance P / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Biphenyl Compounds; 0/Receptors, Neurokinin-1; 0/Receptors, Neurotransmitter; 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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