Document Detail

Discovery of remikiren as the first orally active renin inhibitor.
MedLine Citation:
PMID:  8498974     Owner:  NLM     Status:  MEDLINE    
Angiotensin converting enzyme (ACE) inhibitors are used for the treatment of hypertension and congestive heart failure. However, ACE not only cleaves angiotensin I but is also responsible for the degradation of bradykinin. Therefore, renin inhibitors which block the system at an early step without influence on bradykinin should be devoid of side effects. Since renin has a very strong species specificity, it was necessary to develop new techniques to measure arterial pressure as well as hypertension models in primates in order to select orally active renin inhibitors. Remikiren (Ro 42-5892, CAS 126371-83-3) is a very potent renin inhibitor in vitro (IC50 for human renin = 0.7 nmol/l) and in vivo. Despite short lasting biochemical changes the arterial blood pressure decrease induced by remikiren is very long lasting (over 24 h). Several in vivo experiments have shown that remikiren is specific for renin and does not decrease arterial pressure by an unrelated mechanism. In sodium depleted monkeys, the blood pressure decrease induced by remikiren was similar to the blood pressure decrease induced by cilazapril, an ACE inhibitor. Clinical results seem to confirm the preclinical findings and show that remikiren is indeed a potent orally active renin inhibitor inducing a long lasting blood pressure decrease.
J P Clozel; W Fischli
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  43     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-06-21     Completed Date:  1993-06-21     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  260-2     Citation Subset:  IM    
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
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MeSH Terms
Imidazoles / pharmacology*
Renin / antagonists & inhibitors*
Reg. No./Substance:
0/Imidazoles; 135669-48-6/remikiren; EC

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