K Stoschitzky — Page 3

PubMed1989

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.

Adult↗

PubMedDate not supplied

Stereoselective electrophysiological effects of propafenone in Langendorff perfused guinea pig hearts.

The present study was focused on the stereoselective electrophysiological effects of (R)- and (S)-propafenone.HCl evaluated in isolated Langendorff perfused guinea pig hearts. Conduction intervals were measured using an ECG-recording method of high resolution. Refractory periods of the different parts of the myocardium were determined by stimulation with premature stimuli, as well as by stimulation with increasing pacing rate (rate-dependent/refractory periods). Drug concentrations of 0.1, 1 and 3 microM were tested. Both compounds induced a dose-dependent increase in AV-nodal, His-bundle, and intraventricular conduction time which reached significance (p less than 0.01) following 3 microM of either compound. Sinus rate was also dose-dependently and significantly reduced. (R)- and (S)-propafenone.HCl induced a marked prolongation of the rate-dependent refractory period of sino-atrial (by 140 +/- 22%, p less than 0.01 and by 141 +/- 14%, p less than 0.01, respectively) and AV-nodal (by 34 +/- 22%, p less than 0.01 and by 42 +/- 15%, p less than 0.01, respectively) conduction and of the atrial (by 182 +/- 21%, p less than 0.01 and by 195 +/- 15%, p less than 0.01, respectively) and ventricular (by 93 +/- 16%, p less than 0.01 and by 88 +/- 16%, p less than 0.01, respectively) myocardium. The effective refractory periods evaluated by stimulation with premature stimuli were also significantly prolonged under the influence of (R)- and (S)-propafenone.HCl, except the ventricular myocardial refractoriness by (R)-propafenone.HCl (increase to 114 +/- 23%, n.s.). Both compounds showed a strong rate-dependence of their effects and, thus, the refractory periods evaluated by stimulation with increasing pacing rate were significantly more prolonged than the refractory periods evaluated by stimulation with premature stimuli. The main difference between the effects of (R)- and (S)-propafenone.HCl on the cardiac electrical activity is the lack of effect of (R)-propafenone.HCl on the ventricular myocardial refractoriness evaluated by stimulation with premature stimuli.

Animals↗