Abstract
SAKAI, K., AONO, J., SHIRAKI, Y., HINOHARA, Y., AKAMATSU, A., TANAKA, S. and KUROMARU, K. MC-838 (Altiopril Calcium): A Novel Orally Active Angiotensin Converting Enzyme Inhibitor. Tohoku J. exp. Med., 1987, 152 (4), 363-374 - 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) and 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 (3mg/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.
