Initial evaluation of the non-sulfhydryl-containing converting enzyme inhibitor MK-521 in hypertensive humans.
MK-521 is a new orally active, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor. Single doses of 2.5, 5.0, 10.0, and 20.0 mg were administered to nine hypertensive patients alternating with placebo. All doses of MK-521 caused profound suppression of ACE activity for more than 24 h and decreased standing diastolic blood pressure for more than 12 h without changes in pulse rate. Although there was no further reduction in blood pressure with doses above 5.0 mg, the duration of action was prolonged for more than 24 h with the higher doses. Serum MK-521 concentrations increased with dosage, and ACE was inhibited maximally at concentrations above 10 ng/ml. In this initial study, MK-521 was well tolerated and proved to be a potent and long-acting antihypertensive agent.
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D004151:Dipeptides / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007700:Kinetics; D017706:Lisinopril; D008297:Male; D008875:Middle Aged
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D017706:Lisinopril