Summary
Stereoisomers often exhibit differences in their pharmacological activities. Therefore, the phosphodiesterase inhibitory effects of the cardiotonic agent saterinone in form of the racemate were investigated in comparison with the inhibitory properties of its enantiomers R(+)- and S(−)-saterinone. For this purpose the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts and porcine hearts were separated by DEAE-sepharose anion exchange chromatography. Four different phosphodiesterase isoenzymes were isolated from failing human myocardium and designated phosphodiesterase I–IV. Three phosphodiesterase isoenzymes could be separated from ventricular tissue of porcine hearts. A Ca2+/calmodulin stimulated phosphodiesterase I was not detectable in porcine myocardium.
In failing human hearts racemic saterinone was a potent inhibitor of phosphodiesterase III (IC50 0.02 μmol/l) and IV (IC50 0.03 μmol/l) as compared to the inhibition of phosphodiesterase I (IC50 37.3 μmol/l) and II (IC50 51.4 μmol/l). In comparison with the racemate, R(+)- and S(−)-saterinone showed only slight differences in their phosphodiesterase inhibitory effects. R(+)-saterinone inhibited phosphodiesterase III slightly but significantly more potently and selectively than did S(−)-saterinone. Compared to the inhibition of phosphodiesterase I and II both enantiomers were similarly potent and selective inhibitors of phosphodiesterase III and IV. Similar results were obtained in porcine hearts.
It is concluded that the racemate saterinone and its enantiomers R(+)- and S(−)-saterinone are virtually equipotent concerning the inhibition of phosphodiesterase isoenzymes isolated from failing human hearts or porcine ventricular tissue. The enantiomers of saterinone did not exhibit distinct stereoselectivity in their phosphodiesterase inhibitory effects.
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Correspondence to: W. Zimmermann at the above address
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Zimmermann, W., Scholz, H., Schumacher, C. et al. Effects of saterinone and its enantiomers R(+)-saterinone and S(−)-saterinone on the phosphodiesterase isoenzymes from ventricular tissue of failing human hearts and porcine hearts. Naunyn-Schmiedeberg's Arch. Pharmacol. 349, 611–618 (1994). https://doi.org/10.1007/BF01258467
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DOI: https://doi.org/10.1007/BF01258467