Quinapril: overview of preclinical data

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Drug Development

Background:

• Quinapril hydrochloride is a novel, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor.
• Extensive preclinical studies have evaluated its efficacy and safety in vitro and in vivo.

Purpose of the Study:

• To assess the antihypertensive effects of quinapril in various animal models.
• To investigate its impact on cardiac function and progression of heart failure.
• To evaluate its pharmacokinetic and toxicological profile.

Main Methods:

• In vitro and in vivo animal models, including rabbit aorta and hypertensive rodents and dogs.
• Assessment of contractile and pressor effects of angiotensin I.
• Evaluation of blood pressure reduction and development of tolerance.
• Pharmacokinetic studies on absorption, distribution, metabolism, and excretion.
• Toxicological assessments including teratogenicity, carcinogenicity, and mutagenicity.

Main Results:

• Quinapril inhibited angiotensin I effects and lowered blood pressure in multiple hypertensive models.
• No tolerance was observed in spontaneously hypertensive rats after 14 days of treatment.
• Preliminary data in cardiomyopathic hamsters suggest prevention of left ventricular dysfunction.
• Quinapril is rapidly absorbed, widely distributed (except brain), and hydrolyzed to its active form, quinaprilat.
• Preclinical toxicology is similar to other ACE inhibitors; no teratogenic, carcinogenic, or mutagenic effects were found.

Conclusions:

• Quinapril demonstrates significant antihypertensive activity, likely through inhibition of vascular ACE and reduction of peripheral resistance.
• The drug is well-tolerated with no observed tolerance and possesses a favorable preclinical safety profile.
• Quinapril shows potential in managing hypertension and mitigating cardiac failure progression.