Peculiarities of the effect of antiepileptic drugs on seizures in mice with corneal kindling against the background of low-dose premedication with carbamazepine and sulthiame

Abstract

The aim of the study was to evaluate the effectiveness of antiepileptic drugs (AED) with a different mechanism of action against the background of prior use of low doses of carbamazepine and sultiam in the model of corneal kindling in mice. Materials and methods. The corneal kindling model in mice was used. The convulsive model was reproduced under the parallel preliminary administration of carbamazepine and sulthiame 30 minutes before electrostimulation. The anticonvulsant activity of AED (sulthiame, levetiracetam, carbamazepine, valproate, lamotrigine and retigabine) was studied under conditions after the formation of a stable syndrome of the generalised convulsive activity. Results and discussion. The administration of carbamazepine and sulthiame drugs modulates the activity of the cytochrome P450 enzyme system. Thus, carbamazepine in the dose of 7 and 12 mg/kg showed no significant anticonvulsant activity (the convulsive intensity – 4.42±0.25 points; 4.44±0.32 points) after its preliminary chronic administration, the same doses of carbamazepine showed a noticeable anticonvulsant effect in the control group of animals (3.52±0.26 points; 3.2±0.6 points, respectively). The anticonvulsant activity of lamotrigine changed both in the case of the preliminary chronic administration of an inducer (carbamazepine), and an inhibitor (sulthiame) of the cytochrome P450 system. Conclusion. Changes in the pharmacological effects of AED observed against the background of chronic administration of carbamazepine and sulthiame, in our opinion, may be due to both the modulation of the cytochrome P450 system and other groups of enzymes involved in the AED metabolism.