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  • Title: Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man.
    Author: Stoschitzky K, Lindner W, Rath M, Leitner C, Uray G, Zernig G, Moshammer T, Klein W.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1989 Apr; 339(4):474-8. PubMed ID: 2739756.
    Abstract:
    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.HCl; 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 less than 0.0001) and 40 mg (S)-propranolol.HCl (-32.3%; p less than 0.0001), whereas 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.
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