Document Detail


Discovery of remikiren as the first orally active renin inhibitor.
MedLine Citation:
PMID:  8498974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J P Clozel; W Fischli
Related Documents :
11054234 - Role of neuropeptide y in the development of two-kidney, one-clip renovascular hyperten...
8017664 - Sympathetic neural blockade by thoracic epidural anesthesia suppresses renin release in...
23508484 - Blood pressure measurement: one arm or both arm?
8229794 - The role of the kidney in canine blood pressure control: direct assessment of the close...
7564334 - Effect of gamma 2-melanocyte-stimulating hormone on cerebral blood flow in rats.
7546114 - The effects of non-thermal pulsed electromagnetic energy on wound healing of pressure u...
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    
Affiliation:
Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Imidazoles / pharmacology*
Renin / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Imidazoles; 135669-48-6/remikiren; EC 3.4.23.15/Renin

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


Previous Document:  Acute effects of a pseudo-tetrapeptide as renin inhibitor on blood pressure and renin-angiotensin sy...
Next Document:  Inhibitors of the renin-angiotensin system. Clinical pharmacology studies on kinetics, dynamics and ...