Pharmacological properties of the converting enzyme inhibitor, enalapril maleate (MK-421).

Enalapril maleate (MK-421), an ethyl ester, is an angiotensin-converting enzyme (ACE) inhibitor from a novel series of substituted N-carboxymethyldipeptides. The parent diacid (MK-422) N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro of MK-421 inhibited hog plasma ACE with an I50 of 1.2 nM. Because deesterification occurs slowly or not at all in vitro, the in vitro I50 for enalapril was 1200 nM. However, both enalapril and MK-422 were potent inhibitors of ACE by the i.v. and oral routes in rats and dogs. In rats with experimental hypertension, enalapril was most potent in those models in which the renin-angiotensin system plays a dominant role (salt restriction, two-kidney Grollman) and in models rendered renin dependent by diuretics, although blood pressure reduction did occur in low or normal renin models such as spontaneously hypertensive rats, in which inhibition of ACE as measured by the blockade of angiotensin I pressor responses bore little temporal relationship to the later fall in blood pressure after enalapril.