Comparison of the inotropic effects of some 5 alpha-cardenolides on guinea pig left atria.

The inotropic activity of eleven 5 alpha-cardenolides and six 5 beta-cardenolides was determined using guinea pig left atria and the results were compared with published data obtained from cat toxicity studies. The guinea pig atrial studies showed that the configuration of the A/B ring junction did not influence significantly the cardiotonic potency of digitoxigenin and its 5 alpha-epimer, uzarigenin, but was of significance with respect to the influence of substituent groups. Glucosidation decreased the potency of uzarigenin but increased that of digitoxigenin. By contrast, conjugation with rhamnose increased the activity of both uzarigenin and digitoxigenin. Cat toxicity data did not correlate well with that obtained using guinea pig atria, possibly because of the variable influence of pharmacokinetic factors applicable to the cat toxicity studies.