Inhibition by digoxin and SC4453 of (Na + K)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain

SC4453 is a digoxin analogue with a pyridazine instead of a lactone ring on C_17β. SC4453 was compared with digoxin with respect to inhibition of (Na⁺ + K⁺)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain. SC4453 was slightly less potent than digoxin but showed a similar sensitivity to K⁺. As for cardenolides, species differences in sensitivity to SC4453 were accounted for by differences in the rate of dissociation from the receptors. These observations confirm that the human heart is one of the tissues most sensitive to cardiac glycosides.