title: [Studies on angiotensin I converting enzyme (ACE) inhibitory effect of imidapril. (I). Inhibition of various tissue ACEs in vitro].
abstract: Imidapril is a newly synthesized non-sulfhydryl-containing angiotensin I converting enzyme (ACE) inhibitor. The present study describes the inhibitory effects of imidapril and its active metabolite 6366A on ACEs from various tissues and compares its effects to those of captopril, enalapril and enalaprilat in vitro. 6366A inhibited swine renal and human serum ACEs with an inhibition constant (Ki) of 0.067 nM and 0.04 nM, respectively. These values were 3 to 18 times more potent than those of the other inhibitors. The kinetic study showed that 6366A exerted competitive type inhibition. The ACE inhibition (IC50 values) of 6366A, enalaprilat and the structurally related compounds (6366DM and 6366PY) were compared in homogenates of lung, aorta, heart, brain and kidney from spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). The inhibitory effects of 6366A on all tissue ACEs from SHRs and WKYs were the most potent among these compounds. And the inhibitory potencies of these compounds were correlated with their chemical structure. The present results suggest that 6366A may show a strong inhibitory effect on ACEs from several tissues and species due to its chemical characteristics.
authors.affiliation: Research Laboratories of Applied Biochemistry, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sugaya
authors.forename: S
authors.initials: S
authors.lastname: Minobe
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: M
authors.initials: M
authors.lastname: Kubo
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D002216:Captopril / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013552:Swine
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007093:Imidazoles; D048289:Imidazolidines; D002216:Captopril; C065166:imidapril; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat