STEREOSELECTIVITY IN CARDIOVASCULAR AND BIOCHEMICAL-ACTION OF CALCIUM-ANTAGONISTS - STUDIES WITH THE ENANTIOMERS OF THE DIHYDROPYRIDINE NITRENDIPINE

Objectives: The cardiovascular and biochemical effects of R- and S-nit rendipine were studied in six healthy subjects in a single-blind place bo-controlled study. Methods: After received oral doses of placebo, 20 mg R-, 80 mg R- (n = 5), 20 mg S-, and 20 mg racemic nitrendipine, he art rate, systolic, diastolic, and mean arterial blood pressure, leg b lood flow, peripheral vascular resistance, plasma renin activity, nore pinephrine, epinephrine, dopamine, and aldosterone plasma levels were measured before and up to 3 hours after administration. Results: Neith er placebo nor 20 or 80 mg R-nitrendipine caused significant changes o f cardiovascular and biochemical parameters. After 20 mg S-nitrendipin e and 20 mg racemic nitrendipine, significant changes in diastolic blo od pressure (-9.1/-7.4 mm Hg), heart rate (+21.9/+17.3 beats/min), leg blood flow (+6.8 ml.min(-1).gm tissue(-1)), peripheral vascular resis tance (-16.9 mm Hg.min.gm tissue.ml(-1)), norepinephrine (+476/+281 ng .L(-1)), and plasma renin activity (+9.5/+3.6 ng.ml(-1).hr(-1)) were o bserved. The changes in cardiovascular and biochemical parameters were closely related to the serum S-nitrendipine concentrations. Conclusio ns: It can be concluded that, after administration of the racemate, th e S-enantiomer is responsible for the cardiovascular and biochemical e ffects observed and that S-nitrendipine is at least an order of magnit ude more potent than the R-enantiomer.