Comparison of the inotropic potencies of some synthetic and naturally occurring cardiac glycosides using isolated left atrium of guinea pig.

The inotropic activity of 19 cardioactive steroids was determined using the electrically driven left atrium of the guinea pig. The compounds tested included five alpha-L-rhamnosides and four alpha-L-thevetosides. These were compared with their related genins and with representative examples of beta-D-glycosides. The study showed that rhamnosides and thevetosides were amongst the most active of all cardiac glycosides. The high activity of these compounds was probably related to the alpha-L-glycoside linkage and the configuration of the 4'-hydroxyl group and the 5'-methyl group. There was a stepwise loss of activity when the hydroxyl groups of the sugars were acetylated. The extent to which rhamnose enhanced the potency of different genins varied with the nature of the genin and ranged from 6- to 35-fold. The great variation in the published values for some of the glycosides tested demonstrates the need to standardize methods for testing cardiac glycosides.