Summary
The calcium-antagonistic properties of the novel compound Goe 5438 have been studied in single cardiomyocytes from embryonic (chicken) and adult (guinea-pig) ventricles, in part in comparison with the inhibitory effects of the 1,4-dihydropyridine calcium antagonist nimodipine. Both substances block spontaneous action potentials and contractions of embryonic heart cells at about 0.1 μmol/l. In collagenase-dispersed ventricular cardiomyocytes of guinea-pigs, stereospecific inhibition of the slow calcium current (I ca ) by Goe 5438 was observed at 10 μmol/l by means of voltage-clamp experiments. The (+)-enantiomer of Goe 5438 elicited a stronger inhibition of the slow inward current than the (−)-enantiomer. The frequency dependence of the inhibitory effect of Goe 5438 as well as that of nimodipine could be shown to be negligible in measurements of I Ca and contractions, whereas the inhibitory influence of verapamil, verified in the same experimental arrangement, exhibited a distinct frequency dependence. With respect to a possible potential dependence of the inhibitory effect of Goe 5438 and nimodipine, it could be shown that a hyperpolarization during the course of application of either calcium antagonist produced recovery of the calcium-dependent excitation neither in adult nor in embryonic cells. In adult cardiomyocytes, the dependence of I Ca on the membrane potential was not altered by Goe 5438. It is concluded that the mode of action of Goe 5438 resembles that of 1,4-dihydropyridine calcium antagonists.
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Supported by the Austrian Science Research Fund, grant No. 4662
A preliminary report of some findings has been presented at the 28th Spring Meeting of Deutsche Gesellschaft für Pharmakologie und Toxikologie, Mainz 1987 (Wagner and Koidl 1987)
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Koid, B., Wagner, B. & Tritthart, H.A. The inhibitory effects of the novel calcium antagonist Goe 5438 on calcium-dependent processes of excitation and contraction of single cardiomyocytes. Naunyn-Schmiedeberg's Arch Pharmacol 337, 447–453 (1988). https://doi.org/10.1007/BF00169538
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DOI: https://doi.org/10.1007/BF00169538