ABSTRACT

The cardiotonic steroids include a diverse group of compounds that act on the heart to produce a positive inotropic effect and, in higher concentrations, toxic effects including arrhythmias and cardiac arrest. The expression "digitalis" is often used as a generic term to cover all cardiotonic steroids. In particular, it is usual practice to refer to the receptor for cardiotonic steroids as the "digitalis receptor". Cardiotonic steroids have very narrow therapeutic to toxic ratios, and one of the objectives of structure-activity relationships studies has been to develop glycosides with improved therapeutic ratios. The cardiotonic steroids act on the heart by direct and indirect mechanisms. The direct effects are best demonstrated in isolated heart muscle preparations where the drugs produce both inotropic and toxic effects. D. S. Fullerton et al. used X-ray crystallography, molecular graphics, and molecular mechanics computer programs to compare the structures of digitoxigenin and chlormadinone acetate.