New approaches in the treatment of epilepsy

Introduction. Despite the significant progress made in the treatment of epilepsy in recent years, no less than 30–40% of patients cannot achieve complete cessation of seizures.

Objective. To evaluate new approaches in the epilepsy treatment with nano-sized dosage forms and 3-benzylamino-metilenpirrolidin-2,4-dion (beprodone).

Materials and methods. Evaluation of the anticonvulsant activity of nano-phenazepam in comparison with bromine-dihydrochlorophenyl-benzodiazepine (phenazepam) in substances was carried out. 2-aethylium-6-methyl-3-hydroxypyridine succinate (Mexidol) encapsulated on copolymers of lactic and glycolic acids was chosen as the second medicine for evaluation. Beprodone dosed 100 mg/kg intraperitoneally was the third drug assessed in rats. Chronic cobalt-induced epileptogenic focus was chosen as an experimental model. Additional clinical study of beprodone was conducted in 75 patients with epilepsy (men and women, age ranging 18–65 years) with uncontrolled focal seizures with or without secondary generalization.

Results. In secondary generalized epilepsy model in rats, nanophenazepam significantly reduced epileptiform discharges in the cortex and hypothalamus along with hippocampus. In the chronic model of cobalt epilepsy, nanomexidol reduced the number of epileptiform discharges 3 times and also stopped the status epilepticus (reducing 7.8 times the number of secondary generalized tonic-clonic seizures). The targets for beprodon are cortical foci and, in the second stage, subcortical foci which generate epileptic activity. In 75 patients with epilepsy who had uncontrolled focal seizures with or without secondary generalization, a significant increase in days without seizures was noted on beprodon; the number of seizures decreased 2 times (p <0.01).

Conclusion. Further investigation of new targets for novel antiepileptic drugs and introduction of the latter into clinical practice can be considered as one of the ways to solve the problem of drug resistance.