Digoxin potentiates the anticonvulsant effect of carbamazepine and lamotrigine against experimental seizures in mice

Abstract

The worldwide high amount of multidrug-resistant epilepsy patients makes it urgent to find new approaches to treating, including the use of combinations of classic anticonvulsants with drugs that have an exclusively original mechanism of action, in particular digoxin. The aim of this work was to investigate the influence of low-dose cardiac glycoside digoxin on the anticonvulsant effect of carbamazepine and lamotrigine. Basic models of pentylenetetrazole-induced seizures and electro-induced paroxysms (maximal electroshock [MES]) in mice were used. Classic anticonvulsants were administered intragastrically in conditionally effective and sub-effective doses at 30 min, digoxin – subcutaneously at a dose of 0.8 mg/kg ( 1 / 10 LD 50 ) at 15 min before seizures induction. Pentylenetetrazole at a dose of 80 mg/kg was administered subcutaneously. The MES was reproduced by transmitting an electric current (strength – 50 mA, frequency – 50 Hz) through the corneal electrodes for 0.2 s. It was established that the coadministration of digoxin with carbamazepine and lamotrigine in sub-effective doses renders a marked anticonvulsant action on the model of pentylenetetrazole-induced seizures as well as on seizures induced by MES. Digoxin can reduce the doses of carbamazepine and lamotrigine with a corresponding reduction in the risk of side effects without compromising treatment efficacy.