SYNTHETIC ESTERS OF DIMETHYLAMINOETHANOL EXHIBITING POSITIVE INOTROPIC CARDIAC ACTIVITY

¹ Department of Pharmacology, Harvard Medical School, Boston 15, Massachusetts

The erythrophleum alkaloids, and a series of closely related synthetic alkanolamine esters, were chosen as an appropriate group of compounds for a study of the import of ester conjugation for pharmacodynamic function. In an endeavor to define the structural elements responsible for the marked reinforcement of the positive inotropic cardiac activity of dimethylaminoethanol observed in the case of the naturally occurring alkaloids, dimethylaminoethyl esters of carboxylic acids of diverse types were prepared for appraisal of their ability to improve the volume work capacity of the isolated, failing mammalian heart. As opposed to the indifferent, or toxic nature of the greater number of the synthetic substances tested, the difunctional esters derived from succinic, glutaric, adipic and pimelic acids were found to display a positive inotropie activity of the order of five to ten times that characteristic of the parent alkanolamine, dimethylaminoethanol.