Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man

Summary

In a randomized, double-blind, placebo-controlled, cross-over study 24 healthy volunteers were examined before and 2 h after oral administration of 80 mg (R,S)-, 40 mg (R)- and 40 mg (S)-propranolol · HCI; 8 of them received placebo in an additional run. During exercise on a bicycle ergometer and a rest period the rate pressure product was decreased by 80 mg (R,S)-propranolol · HCl (−32.8%p < 0.0001) and 40 mg (S)-propranolol · HCl (−32.3%;p < 0.0001), whera 40 mg (R)-propranolol · HCl as well as placebo showed no effect. corresponding binding inhibition experiments using (−)-(¹²⁵I)iodocyanopindolol in a sarcolemma-enriched cardiac membrane preparation yielded a eudismic ratio of 179 for (S)- over (R)-propranolol. 2 h after oral application, stereospecific HPLC analysis revealed different individual concentrations in plasma of (R)-(22.3 ± 21.7 ng/ml) and (S)-propranolol (30.4 ± 26.9 ng/ml) when 80 mg of (R,S)-propranolol · Hcl was administered. The plasma levels were similar when 40 mg of the pure enantiomer of (R)- (22.7 ± 20.3 ng/ml) or (S)-propranolol · HCl (28.7 ± 22.5 ng/ml) was applied. (R)- and (S)-propranolol are two substances with different pharmacodynamic and pharmacokinetic properties. As there are methods available to produce the optically pure enantiomers, they should be used rather than the racemic mixture.