Quinapril: overview of preclinical data.
Quinapril hydrochloride, a new, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, has been studied extensively in a variety of in vitro and in vivo animal models. Quinapril inhibits the contractile and pressor effects of angiotensin I in rabbit aorta and in rats, respectively, and lowers blood pressure in both high- and normal-renin rodent and diuretic-treated dog models of hypertension. No tolerance to the antihypertensive effects of quinapril was noted in spontaneously hypertensive rats treated with quinapril for up to 14 consecutive days. As with other ACE inhibitors, quinapril had virtually no effect on the development of hypertension in the renin-independent one-kidney deoxycorticosterone (DOCA)-salt hypertensive rat. Antihypertensive activity best correlates with the inhibition of tissue (vascular) ACE, and thus the reduction in peripheral vascular resistance associated with plasma and tissue ACE most likely accounts for the therapeutic benefit of quinapril. Preliminary data from a trial of quinapril in cardiomyopathic hamsters show that the drug prevents the anticipated decline in left ventricular contractile function and retards the temporal progression of left ventricular failure. ACE inhibitors have been found to have a lipid-neutral profile, unlike some other classes of antihypertensives. Quinapril is rapidly absorbed and extensively distributed to all tissues except brain. It is rapidly hydrolyzed to quinaprilat, its pharmacologically active diacid form. Metabolism to other compounds is not extensive. Quinapril's preclinical toxicologic profile is similar to that of other ACE inhibitors. Long-term toxicology studies show that quinapril is not teratogenic, carcinogenic, or mutagenic.
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
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Kaplan
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Taylor
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Olson
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D006224:Cricetinae; D004341:Drug Evaluation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D000077583:Quinapril