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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 50 (1996), S. 339-342 
    ISSN: 1432-1041
    Schlagwort(e): Key words Propranolol; stereoselectivity ; chirality ; enantiomers ; isomers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Abstract Objective: We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)- and (S)-enantiomers of propranolol. Methods: Blood samples were taken immediately before and at the end of exercise in 12 patients receiving chronic treatment with racemic (R, S)-propranolol. Plasma concentrations of (R)- and (S)-propranolol were determined by HPLC. Results: In contrast to atenolol, mean plasma concentrations of (S)-propranolol were significantly higher (+20%) than those of (R)-propranolol at rest. During exercise there was an increase in plasma concentrations of both (R)-propranolol (+129%) and (S)-propranolol (+109%). Conclusion: Based on information from in vitro studies we conclude that the increase in plasma concentrations of (S)-propranolol during exercise is caused by a release of the drug from adrenergic nerves, whereas the reason for the increase in (R)-propranolol remains to be determined. This release of the β-adrenoceptor blocking (S)-enantiomer directly at the synaptic gaps might be one reason for the poor correlation between plasma concentration and effect of β-adrenoceptor antagonists repeatedly described in the literature.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1435-1803
    Schlagwort(e): propafenone·HCl ; enantiomers ; cardiac conduction andrefractoriness ; isolated guinea pig heart ; Langendorff perfused
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary 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 μM were tested. Both compounds induced a dose-dependent increase in AV-nodal, His-bundle, and intraventricular conduction time which reached significance (p〈0.01) following 3 μM 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〈0.01 and by 141±14%, p〈0.01, respectively) and AV-nodal (by 34±22%, p〈0.01 and by 42±15%, p〈0.01, respectively) conduction and of the atrial (by 182±21%, p〈0.01 and by 195±15%, p〈0.01, respectively) and ventricular (by 93±16%, p〈0.01 and by 88±16%, p〈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 refratoriness evaluated by stimulation with premature stimuli.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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