Toward the discovery of digitalis derivatives with inotropic selectivity

Increased incidence and prevalence of congestive heart failure make the discovery of novel positive inotropes (i.e. agents that increase the peak force of contraction of the heart muscle) a priority. Cardiac glycosides currently in use are inadequate for effective treatment or even for the minimization of the associated discomfort and disability. These drugs also frequently cause dangerous toxic effects. Substantial research within the pharmaceutical industry has failed to identify a nonsteroidal ‘digitalis replacement’. Hence, every effort should be made to create new positive inotropes. This review departs dramatically from the current thinking on the problem and reveals a new approach to the discovery of novel cardiotonic drugs with inotropic selectivity.