Document Detail


Effects of the renin inhibitor N-[N-(3-(4-amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histid inyl] -(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2-amide acetate in anesthetized rhesus monkeys.
MedLine Citation:
PMID:  7945514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The renin inhibitory effect of the non-peptide renin inhibitor S 2864 (N-[N-(3-(4-Amino-1-piperidinyl-carbonyl)-2(R)-benzylpropionyl)-L- histidinyl]-(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6(2-pyridyl)-hexane-2- amide acetate, CAS 135683-92-0) was characterized in vitro and in vivo in primates. In vitro, S 2864 inhibited the activity of purified human plasma renin with an IC50 of 3.8 x 10(-10) mol/l and did not affect related human aspartyl proteases like human cathepsin E, cathepsin D or pepsin. In vivo, in anesthetized sodium depleted rhesus monkeys S 2864 decreased mean arterial blood pressure after intraduodenal (i.d.) administration of 2 mg/kg significantly by 27% from 94 +/- 8 to 62 +/- 6 mmHg for 90 min. Heart rate was not changed. Cumulative intravenous (i.v.) administration of S 2864 or remikiren in doses of 1, 10 and 30 micrograms/kg significantly decreased systemic blood pressure, dP/dtmax and cardiac output while heart rate was not changed. Plasma angiotensin II (ANG II) levels as well as renin activity were dose dependently reduced after 10, 30 and 60 min. It is concluded that S 2864 is an effective specific inhibitor of human renin eliciting marked blood pressure lowering activities in primates.
Authors:
W Linz; H Heitsch; R Henning; W Jung; H W Kleemann; W U Nickel; D Ruppert; H Urbach; A Wagner; B A Schölkens
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  44     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-10-25     Completed Date:  1994-10-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  815-20     Citation Subset:  IM    
Affiliation:
Hoechst Aktiengesellschaft, Strategic Business Unit (SBU) Cardiovascular Agents, Frankfurt/Main, Fed. Rep. of Germany.
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MeSH Terms
Descriptor/Qualifier:
Anesthesia
Angiotensin II / blood
Angiotensin-Converting Enzyme Inhibitors / pharmacology
Animals
Cattle
Chymotrypsin
Dogs
Female
Guinea Pigs
Hemodynamics / drug effects
Humans
Hydrolysis
Macaca mulatta
Male
Oligopeptides / pharmacology*
Peptidyl-Dipeptidase A / blood
Protease Inhibitors / pharmacology
Rats
Rats, Wistar
Renin / antagonists & inhibitors*,  blood
Sheep
Species Specificity
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Oligopeptides; 0/Protease Inhibitors; 11128-99-7/Angiotensin II; 150739-46-1/S 2864; EC 3.4.15.1/Peptidyl-Dipeptidase A; EC 3.4.21.1/Chymotrypsin; EC 3.4.23.15/Renin

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


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