Possible mechanism of digoxin-induced convulsions

Intraventricular (IVT) administration of digoxin (7.5 micrograms) induced 'popcorn-type' convulsions in rats. Though the convulsions looked similar to morphine-induced seizures, naloxone failed to antagonize these effects. Other anticonvulsants like phenobarbitone, ethosuximide, or GABAergic substances like piracetam and semicarbazide also had no protective effect against digoxin-induced convulsions. While calcium chloride potentiated these effects of digoxin, phenytoin, magnesium chloride, and potassium chloride treatment showed blocking actions. These observations suggest the involvement of Na/K-ATPase system in digoxin-induced convulsions. Clonidine and diazepam also provided protection against digoxin-induced convulsions through an unknown mechanism.