The anticonvulsant effect of digoxin on basic models of primary generalized seizures does not depend on the route of administration

Abstract

Improving the prevention and treatment of epilepsy is one of the urgent tasks. Based on the available data on the anticonvulsant activity of the cardiac glycoside digoxin, it is advisable to compare the anticonvulsant effect of the drug by different routes of administration in the experiment. Aim. To determine the impact of the route of administration on the anticonvulsant effect of the cardiac glycoside digoxin on basic models of primary generalized seizures induced by pentylenetetrazol and maximal electric shock. Materials and methods. Two basic models were used: the model of primary generalized convulsions induced in mice by pentylenetetrazol (80 mg/kg subcutaneously) and maximal electric shock (current strength – 50 mA, frequency – 50 Hz, 0.2 sec corneally). Digoxin was administered in the dose of 0.8 mg/kg (about 1/10 LD50) 30 min before modeling seizures in the stomach and subcutaneously. Standard parameters of convulsive syndrome severity and mortality were recorded. Results and discussion. In both seizure models, the anticonvulsant effect of digoxin was little dependent on the route of administration. In the pentylenetetrazole-induced model, with both routes of administration, lethality tended to decrease; when administered intragastrically, digoxin statistically significantly reduced the number of clonic-tonic seizures per 1 mouse, the number of animals with the most severe tonic seizures, and the duration of the convulsive period; when administered subcutaneously, it significantly increased the latent period of seizures and reduced the number of animals with tonic seizures. In the model of maximal electric shock, digoxin reduced seizure severity andlethality almost equally by both routes of administration (by 55 % with the intragastric administration and by 67.5 % with the subcutaneous administration). In both models, there were no statistically significant differences in the course of seizures in both routes of the digoxin administration. With subcutaneous administration, the anticonvulsant effect was somewhat more pronounced at the level of a weak tendency. Conclusions. The anticonvulsant effect of digoxin when administered intragastrically and subcutaneously in mice with models of pentylenetetrazole-induced seizures and maximal electric shock is practically independent of the routeof administration. Digoxin has a pronounced anticonvulsant effect on the model of electrically induced seizures, and a moderate effect on the model of pentylenetetrazole seizures.