ASI-222,3beta-O-(4-amino-4,6-dideoxy-beta-d-galactopyranosyl)
digitoxigenin, is a semi-synthetic
cardiac glycoside patterned after a natural
glycoside obtained from Cambodia. Effects of
ASI-222 on contractile force in the isolated rabbit atria, cardiac contractile force, cardiac rate, ventricular excitability and functional refractory period in dogs, and acute toxicity in mice have been compared to those effects of
ouabain. Both electrically driven and spontaneously beating atria demonstrated more rapid onset and greater maximum increases in contractile force with
ASI-222 than with
ouabain in equal bath concentrations. In the dog,
ASI-222 increased cardiac contractile force more rapidly and at a lower cumulative dose than
ouabain. Moreover, the maximum increase in contractile force obtained with
ASI-222 was greater than that obtained with
ouabain. The occurrence of
ventricular ectopic beats was observed at a higher cumulative dose of
ASI-222 than for
ouabain. Also,
ASI-222 produced a decrease in ventricular excitability and an increase in functional refractory period ot the ventricle.
Ouabain, in the same molar dose, produced either no change or a slight increase in these parameters. Our data indicate that
ASI-222 has a greater therapeutic index than
ouabain. This difference may be partially explained by effects of
ASI-222 on electrical properties of the heart.