CARDIOTONIC STEROIDS: CORRELATION OF SODIUM-POTASSIUM ADENOSINE TRIPHOSPHATE INHIBITION AND ION TRANSPORTin vitroWITH INOTROPIC ACTIVITY AND TOXICITY IN DOGS

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Abstract
1. A new series of cardiotonics based on five steroid nuclei has been evaluated for inhibition of Na-+/K-+-ATPase and Rb uptake by red blood cells, and for inotropic activity and toxicity in dogs. Structure-activity relationships are discussed. 2. The in vitro tests can be used satisfactorily to predict inotropic activity, but not toxicity or therapeutic ratio. 3. Although compounds with greatly improved therapeutic ratios relative to ouabain and tolusin have been obtained, they proved to be strongly emetic in the conscious dog.