Delapril is a carboxy-alkyl-
dipeptide mainly converted in animals and humans to an active diacid derivative (M-I), which in turn is converted to an active 5-hydroxy-indane diacid (M-III). In humans these metabolites are excreted in the urine. The presence of the indanyl-
glycine moiety gives
delapril a high lipophilicity, greater than several other
angiotensin-converting enzyme (
ACE) inhibitors, such as
captopril and
enalapril. Due to its greater lipophilicity,
delapril has been shown to exert a more effective inhibition of vascular ACE than
captopril and
enalapril, both in vitro and in vivo. The activity of
delapril on tissue ACE also lasts longer than on the circulating
enzyme. At doses ranging from 1-10 mg/kg orally,
delapril exerts a marked and long-lasting
antihypertensive action in various experimental models of
hypertension. The blood pressure reduction has been shown to be accompanied by suppression of
angiotensin II release from the vascular wall. In
stroke-prone spontaneously hypertensive rats (SHR-SP) and in SHR with
chronic renal failure, besides reducing
hypertension,
delapril significantly improves survival rate and prevents the development of
stroke,
cardiac hypertrophy, and renal
sclerosis. The ability of
delapril to reduce
hypertrophy in vascular and cardiac tissue has been demonstrated in both in vitro and in vivo experiments.