MC-838 (altiopril calcium): a novel orally active angiotensin converting enzyme inhibitor.
MC-838, calcium (-)-N-[(S)-3-(N-cyclohexylcarbonyl-D-alanyl) thio]-2-methylpropionyl]-L- prolinate, is a new orally active angiotensin converting enzyme (ACE) inhibitor in which the mercapto-group is taken up in a stable thiolester linkage. The linkage was relatively resistant against enzymatic hydrolysis by rat liver homogenates. The ACE prepared from rabbit lung was inhibited by MC-838 in a concentration-dependent manner. In isolated rat aortic ring and guinea-pig ileum preparations, MC-838 was highly specific in suppressing the contractile response to angiotensin-I (A-I) an in augmenting the contractile one to bradykinin. However, the ACE inhibitory activity of MC-838 was 30-100 times less potent than that of captopril. In conscious two-kidney (2 KG), renal hypertensive rats and spontaneously hypertensive rats (SHRs), MC-838 (3 and 10 mg/kg) given orally caused a long-lasting hypotensive effect with a slow onset. When compared on a weight basis (3 mg/kg), the antihypertensive effect of MC-838 was comparable to that of captopril in magnitude, but the duration of action of MC-838 was approximately 2 times longer than that of captopril.
Sakai
K
K
New Drug Research Laboratories, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Aono
J
J
Shiraki
Y
Y
Hinohara
Y
Y
Akamatsu
A
A
Tanaka
S
S
Kuromaru
K
K
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000201:enzymology; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000201:enzymology; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; C048961:MC 838; D011392:Proline