Pharmacological properties of the new non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline.
AB-47 (N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline) is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with omega-aminoalkyl group. AB-47 was slightly more potent than enalaprilat in inhibiting rabbit lung ACE. The ACE inhibition and bradykinin (BK) potentiation by AB-47 in guinea-pig ileal longitudinal muscle were as potent as with enalaprilat. In conscious rat, AB-47 (i.v.) inhibited angiotensin I (A-I)-induced pressor response and augmented BK-induced depressor response more potently and in a long-lasting manner than enalaprilat. Furthermore, AB-47 exhibited higher selectivity for ACE inhibition than for BK inactivation and higher selectivity than enalaprilat and captopril. The inhibition of A-I-induced pressor response by AB-47 (p.o.) was as potent as that of enalapril. These results suggest that AB-47 is a highly potent, long-lasting and relatively A-I-selective ACE inhibitor.
Shirota
M
M
Central Research Laboratories, Asahi Breweries, Ltd., Tokyo, Japan.
Kajiwara
Y
Y
Iijima
M
M
Kitabatake
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D004656:Enalapril / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; C065126:N-(8-amino-1-carboxyoctyl)-alanyl-proline; D004656:Enalapril; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D001920:Bradykinin