Nicardipine, nitrendipine, and bepridil: new calcium antagonists for cardiovascular disorders

The chemistry, pharmacology, pharmacokinetics, clinical uses, and adverse effects of nicardipine, nitrendipine, and bepridil are reviewed. Nicardipine, nitrendipine, and bepridil are calcium antagonists under investigation for the treatment of cardiovascular disorders. Nicardipine and nitrendipine share a common dihydropyridine nucleus with the calcium antagonist nifedipine; bepridil is unrelated to other known calcium antagonists. Like nifedipine, nicardipine and nitrendipine produce peripheral vasodilation as their predominant in vivo effect. Bepridil has vascular, sinoatrial and atrioventricular nodal, and myocardial effects qualitatively similar to those of the calcium antagonist verapamil; it also interferes with the fast sodium channel and prolongs refractoriness in atrial and ventricular tissue. Nicardipine and nitrendipine undergo extensive first-pass hepatic extraction after oral administration; oral bioavailability of bepridil is about 60%. All three drugs are highly protein bound and have been reported to increase plasma digoxin concentrations. Both nicardipine and nitrendipine are effective antihypertensive agents used alone or combined with diuretics, beta blockers, or angiotensin-converting enzyme inhibitors. Nicardipine and bepridil effectively control angina, and preliminary studies indicate that nitrendipine has antianginal properties. Bepridil may be useful in the treatment of various cardiac arrhythmias; however, its tendency to cause or worsen cardiac arrhythmias and its association with torsade de pointes may limit its usefulness. Nicardipine and nitrendipine have similar adverse effect profiles, with vasodilation-related complaints being most common. Since nicardipine, nitrendipine, and nifedipine are similar in efficacy and safety, the eventual availability of sustained-release dosage forms may determine how these drugs are ultimately used. Bepridil is an effective antianginal drug, but, because of its proarrhythmic potential, it should probably not be used as a first-line agent.