ISSN:
1432-1912
Keywords:
(±)-Sotalol
;
(+)-Sotalol
;
(−)-Sotalol
;
Monophasic action potential duration
;
β-Adrenoceptor affinity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The racemate (±) and the two enantiomers of sotalol were studied with regard to the effects on cardiac repolarization. In addition, the affinity to cardiac β-adrenoceptors was investigated for the enantiomers. The effect on left ventricular monophasic action potential duration was assessed in the isolated perfused guinea-pig heart and the β-adrenoceptor affinity of the compounds was studied, using α1- radioligand binding technique, in cellular membranes prepared from the left ventricular free wall of the cat. Moreover, the β-adrenoceptor blocking potency of (+)-sotalol was studied in isolated strips of guinea-pig papillary muscles. Both the racemate and the two enantiomers of sotalol caused α1- concentration-dependent prolongation of the ventricular monophasic action potential duration. The maximal effect and the concentration causing half maximal effect (EC50 = 13 μmol/l) were similar for the racemate and the enantiomers, indicating lack of stereoselectivity for this effect. The β-adrenoceptor affinity (equilibrium dissociation constant) of (+)-sotalol was 11 μmol/l and 4 μmol/l as estimated by the binding technique and in the isolated muscle strips, respectively. The affinity for (−)-sotalol, estimated by binding, was 0.6 μmol/l. Thus, at concentrations of (+)-sotalol required for α1- significant prolongation of cardiac repolarization, this isomer may cause significant β-blockade. In this study the enantiomeric purity was better than 98%, so that the degree of β-blockade may be even more pronounced if the enantiomeric purity of the (+)-enantiomer is less than 98%.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169733
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