Abstract

1. The behavior of 4 synthetic esters of k-strophanthidin, the acetate, propionate, butyrate, and benzoate, was explored in a group of patients with auricular fibrillation and heart failure.

2. A study was made of their potency, speed of action by intravenous injection, persistence of action, absorption from the gastro-intestinal tract, and toxic effects.

3. The relative potencies of the esters by intravenous injection in cats and by intravenous injection in man are similar.

4. The esters produce essentially the same kind of effects as the digitalis glycosides in man. In doses corresponding to those of the digitalis glycosides, they slow the ventricular rate in auricular fibrillation, and produce nausea and vomiting by both a systemic action and a local action in the gastro-intestinal tract. There is indication that in suitable doses they may exert a similar action on the symptoms of heart failure.

5. The esters develop their full action after intravenous injection in man, more rapidly than the digitalis glycosides in common use, namely, within 10 to 30 minutes.

6. The persistence of action of the esters is brief, the effects wearing off within a few hours. There is indication, although this point is in need of further study, that the benzoate persists somewhat longer than the others.

7. The absorption of the acetate and propionate from the gastro-intestinal tract of man appears to be negligible. The butyrate shows fairly rapid absorption, producing its full effects within about an hour, although the ratio of the oral to intravenous dose for a similar effect resembles that of digitalis. The benzoate is unusually well absorbed, and there is indication that its absorption may be nearly complete, approximating the behavior of digitoxin in this respect.

8. Although the glycosides of the strophanthus group are so poorly absorbed from the gastro-intestinal tract as to preclude their use by oral administration, some of the esters of their aglycones are better absorbed than most of the glycosides of the digitalis series. Their speed of action offers interesting possibilities for application in cardiac therapy. The esters deserve more extensive investigation.

These studies were supported in part by the Digitalis Fund of Cornell University Medical College, which includes contributions from Eli Lilly and Company, Wyeth, Inc., Lederle Laboratories, Inc., E. R. Squibb & Sons, Varick Pharmacal Co., The Wm. S. Merrell Company, and the David, Josephine, and Winfield Baird Foundation.