[Pharmacologic study of a semisynthetic digitalis derivative lacking the hydroxyl group on position 14 of the steroid...

All natural cardiac glycosides (CG) have a hydroxyl (OH) group attached to carbon 14 (C 14) of the steroid nucleus which has been considered important for their pharmacological action. To investigate the relation between chemical structure and biological activity of CG, we studied the cardiac effects of a semisynthetic derivative if gluco-digitoxigenin that lacks the C 14 hydroxyl group; the compound was named Dig-3 and corresponds to the number of a series of semisynthetic glycosides being studied. On the failing heart of the Starling's heart-lung preparation Dig-3 reverts experimental cardiac failure. Electrophysiological experiments in anesthetized dogs (morphine chloralose) have shown that Dig-3 shortens the functional refractory period of the ordinary atrial myocardium (OAM), and lengthens that of the specialized atrial tissue (SAT). The basal excitability is reduced in both tissues, however OAM is more susceptible to Dig-3 action. The conduction velocity of impulses in SAT diminishes 50% with one tenth of the lethal dose (LD) of Dig-3 whereas in the OAM, an equivalent decrease is achieved with 60% of LD. A-V dissociation induced by the infusion of toxic doses of Dig-3 reverted to sinus rhythm in about 6 min after the administration was stopped. We conclude that the presence of the OH group attached to C 14 of digitalis molecule does not constitute a structural requirement for the preservation of its inotropic and electrophysiological actions on the heart, although its potency is greatly diminished.