Stereoselective hemodynamic effects of (R)-and (S)-propranolol in man.
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.
Stoschitzky
K
K
Medizinische Universitätsklinik Graz, Department Kardiologie, Austria.
Lindner
W
W
Rath
M
M
Leitner
C
C
Uray
G
G
Zernig
G
G
Moshammer
T
T
Klein
W
W
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D020120:Iodocyanopindolol; D008297:Male; D008566:Membranes / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives; D011433:Propranolol / Q000494:pharmacology*; D011897:Random Allocation; D012508:Sarcolemma / Q000378:metabolism; D013237:Stereoisomerism
D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol