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Angiotensin I‐converting enzyme (ACE) inhibition and antihypertensive effects of EU‐5476, a new, potent, and long‐acting ACE inhibitor
Author(s) -
Huang Chau Ting,
Brooks Robert R.,
Pong Schwe Fang,
Skuster James R.,
White Ralph L.,
Moore Alan F.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430070205
Subject(s) - enalapril , captopril , angiotensin converting enzyme , ace inhibitor , enzyme inhibitor , chemistry , pharmacology , oral administration , blood pressure , angiotensin ii , renin–angiotensin system , plasma renin activity , endocrinology , enalaprilat , enzyme , medicine , biochemistry
EU‐5476 is a new, orally active angiotensin I‐converting enzyme (ACE) inhibitor. In vitro, EU‐5476 produced a concentration‐dependent inhibition of ACE purified from rabbit lung (IC 50 = 0.084 μ). Inhibition showed complex kinetics and was reversible as determined by equilibrium dialysis. EU‐5476 inhibited plasma ACE in mice (93.8% inhibition at 5 μmol/kg) and produced dose‐dependent inhibition of plasma ACE in dogs (ID 50 = 2.52 μmol/kg) after oral administration. In acute aortic coarctate hypertensive rats, EU‐5476 administered orally produced dose‐dependent decreases in blood pressure (ED 30 = 0.53 μmol/kg). The magnitude and duration of blood pressure reduction in hypertensive rats were similar to those of plasma ACE inhibition in dogs, suggesting that plasma ACE inhibition per se is one of the mechanisms of the antipertensive action of EU‐5476. Comparative studies showed that EU‐5476, like enalapril, was more potent and longer acting than captopril in producing plasma ACE inhibition and an antihypertensive response. EU‐5476 is a potent and long‐acting, orally effective ACE inhibitor potentially useful in the treatment of hypertension.