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PubMed1977

The influence of polar and non-polar digoxin and digitoxin metabolites on the 86Rb-uptake of human erythrocytes and the contractility of guinea pig papillary muscles.

The potency of various digoxigenin and digitoxigenin derivatives with different polarity was tested in two biological systems: First, in an 86-Rb-erythrocyte assay which allows to determine the influence on active cation transport (measured as the glycoside concentration exerting half maximal inhibition of 86-Rb-uptake of human erythrocytes = IC50). Second, with isolated guinea pig papillary muscle, which allows to determine glycoside effects on contractile force (measured as the glycoside concentration exerting 100% increase of contractile force = C+100%). The IC50 of the substances covered a range from 3.2 to 4800 X 10(-9) M, the C+100% from 0.7 to 978 X 10(-6) M. In both assay systems the glucuronides of glycosides and genins were between 1.4 and 11 times less potent than the original substances. A highly significant correlation (p less then 0.0001) was found between IC50 and C+100% (r = 0.9996) and between log IC50 and log C+100% (r = 0.9819), the slope for the latter correlation being nearly unite (= 0.9912). The results support the hypothesis that inhibition of active cation transport is and important step in glycoside incuced posite-inotropic effect.

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