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Selected Publication:
Stoschitzky, K; Klein, W; Stark, G; Stark, U; Zernig, G; Graziadei, I; Lindner, W.
Different stereoselective effects of (R)- and (S)-propafenone: clinical pharmacologic, electrophysiologic, and radioligand binding studies.
Clin Pharmacol Ther. 1990; 47(6):740-746
Doi: 10.1038/clpt.1990.102
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- Leading authors Med Uni Graz
- Stoschitzky Kurt
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- Abstract:
- Propafenone is a class 1c antiarrhythmic agent with moderate beta-blocking activity as a result of a structural similarity to beta-adrenoceptor antagonists. In a randomized, double-blind crossover exercise study, eight healthy volunteers were examined before and 2 1/2 hours after oral administration of 300 mg (R,S)-, 150 mg (R)-, and 150 mg (S)-propafenone hydrochloride. The mean rate pressure product was significantly reduced by (R,S)-propafenone hydrochloride (-5.2%; p = 0.045) and half-dosed (S)-propafenone hydrochloride (-5.9%; p = 0.013), whereas the (R)-enantiomer caused no significant changes. There was a significant difference between the effects of (R)- and (S)-propafenone (p = 0.033). In beta-adrenoceptor-binding inhibition experiments with (S)-(125I)iodocyanopindolol in a sarcolemma-enriched cardiac membrane preparation, the eudismic ratio of (S)- over (R)-propafenone was 54. On the spontaneously beating Langendorff-perfused guinea pig heart, 3 x 10(-6) mol/L of both (R)- and (S)-propafenone resulted in significant changes (p less than 0.01) on His bundle conduction (+79% +/- 27% and +69% +/- 9%), as well as comparable decreases in the maximal rate of pacing with 1:1 conduction of the atrial (-54% +/- 10% and -57% +/- 8%) and ventricular myocardium (-42% +/- 6% and -43% +/- 6%), indicating equal effects in sodium channel-dependent antiarrhythmic class 1 activity. Thus (R)- and (S)-propafenone exert different beta-blocking actions but equal effects on the sodium channel-dependent antiarrhythmic class 1 activity. More specific antiarrhythmic class 1 therapy with reduction of beta-blocking side effects may be attained with optically pure (R)-propafenone hydrochloride instead of the currently used racemic mixture.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Oral -
- Adult -
- Animals -
- Double-Blind Method -
- Electrophysiology -
- Exercise Test -
- Female -
- Guinea Pigs -
- Heart - drug effects
- Heart Rate - drug effects
- Hemodynamics - drug effects
- Humans - drug effects
- Iodocyanopindolol - drug effects
- Male - drug effects
- Pindolol - analogs and derivatives
- Propafenone - administration and dosage
- Radioligand Assay - administration and dosage
- Random Allocation - administration and dosage
- Receptors, Adrenergic, beta - metabolism
- Stereoisomerism - metabolism