Objectives: The cardiovascular and biochemical effects of R- and S-nitrendipine were studied in six healthy subjects in a single-blind placebo-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, heart rate, systolic, diastolic, and mean arterial blood pressure, leg blood flow, peripheral vascular resistance, plasma renin activity, norepinephrine, epinephrine, dopamine, and aldosterone plasma levels were measured before and up to 3 hours after administration.
Results: Neither placebo nor 20 or 80 mg R-nitrendipine caused significant changes of cardiovascular and biochemical parameters. After 20 mg S-nitrendipine and 20 mg racemic nitrendipine, significant changes in diastolic blood 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 resistance (-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 observed. The changes in cardiovascular and biochemical parameters were closely related to the serum S-nitrendipine concentrations.
Conclusions: It can be concluded that, after administration of the racemate, the S-enantiomer is responsible for the cardiovascular and biochemical effects observed and that S-nitrendipine is at least an order of magnitude more potent than the R-enantiomer.
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