Alteration of digoxin toxicity by 6-hydroxydopamine and soironolactone

The possibility that the Na+-K+ ATPase of cardiac adrenergic neurons is the toxic receptor site of cardiac glycosides was investigated by performing a chemical sympathectomy in dogs using 6-hydroxydopamine to destroy the adrenergic neurons. No alteration was seen in the therapeutic, toxic, or lethal dose of digoxin after the administration of 6-hydroxydopamine, indicating that the toxic receptor of digoxin is not located on the adrenergic nerve endings. Pretreatment of control dogs with spironolactone increased the toxic and lethal dose of digoxin without changing the therapeutic dose of digoxin. However, spironolactone pretreatment of chemically sympathectomized dogs produced an increase pretreatment of chemically sympathectomized dogs produced an increase in the therapeutic, toxic, and lethal doses of digoxin. Therefore, the destruction of this neuronal tissue decreases the therapeutic effectiveness of digoxin in the presence of spironolactone, and abolishes the ability of spironolactone to alter the therapeutic ratio of digoxin.