Additive suppression of tonic-clonic seizures in mice receiving the combination of carbamazepine, phenobarbital and valproate.

Introduction. Polytherapy with three antiepileptic drugs (AEDs) is used in patients who have seizure episodes classified by physicians and neurologists as refractory or drug-resistant. Although doctors can prescribe these patients 25 various AEDs, no algorithms are available which allow them to choose the most efficacious combinations of AED. Objective. The aim of this study was to isobolographically classify interaction among three classical AEDs (carbamazepine, phenobarbital and valproate), applied in the fixed-ratio combination of 1:1:1, in the maximal electroshock-induced seizures in mice. Materials and method. The anti-seizure activity of the mixture of carbamazepine, phenobarbital and valproate (in the fixed-ratio of 1:1:1) was determined in maximal electroshock-induced seizures - an experimental model of tonic-clonic seizures in mice using type I isobolographic analysis. Results. The mixture of carbamazepine, phenobarbital and valproate (in the fixed-ratio of 1:1:1) produced additive interaction in the maximal electroshock-induced seizure model in mice. The experimentally-derived median effective dose (ED50 exp value) for the mixture was 94.35 mg/kg, whereas the theoretically additive median effective dose (ED50 add value) amounted to 116.77 mg/kg. Conclusions. Although the combination of carbamazepine, phenobarbital and valproate exerted additivity in the mouse maximal electroshock-induced seizure model, it could be recommended for the treatment of patients, if the results of this study would be directly transposed to clinical settings. [ABSTRACT FROM AUTHOR]