Unique pharmacologic properties of amlodipine

Abstract

Amlodipine is an intrinsically long-acting, vasoselective calcium antagonist structurally related to nifedipine, but with unique binding and pharmacologic properties that distinguish it from other agents of this class. Pharmacokinetic studies in animal models demonstrate a more prolonged half-life, high volume of distribution, and gradual elimination of amlodipine compared with that of other calcium antagonists. The presence of a basic side chain at the 2-position of the dihydropyridine ring renders the molecule > 90% ionized at physiologic pH and is believed to be primarily responsible for its markedly different pharmacologic and pharmacokinetic properties. Amlodipine has slow receptor binding kinetics that result in a gradual onset of action and may allow for less dependence on instantaneous plasma levels. Although amlodipine appears to bind to additional calcium channel recognition sites blocked by diltiazem and verapamil, it does not significantly depress heart rate nor does it produce significant negative inotropic effects or electrophysiologic disturbances. Preclinical studies indicate that amlodipine is a potent antihypertensive agent with natriuretic and diuretic properties that may enhance its ability to reduce blood pressure without attendant fluid retention.