Low-Dose Digoxin is Associated with Anticonvulsant Effect Enhancement of Classical Antiepileptic Drugs in the Electro-Induced Seizures in Mice

Abstract

The aim of the study was to determine the effect of low doses of cardiac glycoside digoxin on the anticonvulsant effect of five classical antiepileptic drugs, sodium valproate, topiramate, levetiracetam, clonazepam and phenobarbital, under experimental seizures in mice. Antiepileptic drugs were administered 30 min before to seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate – at doses of 300 and 150 mg/kg; levetiracetam – at doses of 100 and 50 mg/kg; phenobarbital – at doses of 20 and 10 mg/kg; clonazepam – at doses of 0.1 and 0.05 mg/kg body weight. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Maximal electroshock seizure model was reproduced by transmitting an electric current (strength – 50 mA, frequency – 50 Hz) through the corneal electrodes for 0.2 sec. It was found that low-dose digoxin potentiates the anticonvulsant effects of sodium valproate, topiramate and phenobarbital as well as modulates the effects of levetiracetam and clonazepam, showing a distinct pharmacological effect of their sub-effective doses and increasing their therapeutic potential even under incomplete seizure control – the equivalent of drug-resistant epilepsy. The obtained results substantiate the expediency of further study of digoxin as an anticonvulsant drug in the adjuvant therapy of epilepsy and other seizure conditions.