Authors' contribution Wkład autorów: A. Study design/planning zaplanowanie badań B. Data collection/entry zebranie danych C. Data analysis/statistics dane-analiza i statystyki D. Data interpretation interpretacja danych E. Preparation of manuscript przygotowanie artykułu F. literature analysis/search wyszukiwanie i analiza literatury G. Funds collection zebranie funduszy Summary Background. It is estimated that approximately 1% of people worldwide suffer from epilepsy. Currently available antiepileptic drugs (AEDs) are able to control epileptic seizures in about 70% of cases. In the remaining patients (30%), the application of two or three AEDs in combination is necessary for effective seizure management. The goal of this work was to characterize the interaction of three AEDs: lacosamide (lCM), carbamazepine (CBZ) and valproate (VPA) at the fixed-ratio of 1:1:1 in the mouse tonic-clonic seizure model. Material and methods. Male albino Swiss mice, after receiving a combination of lCM, CBZ and VPA, were challenged with electric current to evoke tonic hind limb extension (seizure activity). Protection of the mice from tonic-clonic seizures was assessed by isobolographic analysis to determine the type of interaction occurring between these drugs. Results. Type I isobolographic analysis revealed that the combination of lCM, CBZ and VPA produced infra-additive (antagonistic) interaction in the mouse tonic-clonic seizure model. Conclusions. Since the three-drug mixture of lCM, CBZ and VPA exerted an antagonistic interaction in the tonic-clonic seizure test in mice, we would caution physicians against treating epilepsy patients with this unfavorable combination.

Introduction. Assessment of interactions among antiepileptic drugs (AEDs) during polytherapy is still a challenging issue for physicians and epileptologists worldwide. In spite of 25 currently licensed AEDs, there are no algorithms allowing a proper choice of these drugs to create combinations which would offer epileptic patients an efficacious therapy in the case of seizures refractory to monotherapeutic use of the AEDs. To characterize a type of interaction for a three-drug mixture of oxcarbazepine (OXC), pregabalin (PGB) and topiramate (TPM) in an experimental model of tonic-clonic seizures, an isobolographic analysis of interaction was applied. Materials and Method. The anticonvulsant effects of the three-drug mixture of OXC, PGB and TPM with respect to suppression of tonic-clonic seizures in mice were assessed in the mouse maximal electroshock-induced seizure model. Type I isobolographic analysis was used to characterize the type of interactions among three AEDs. Potential acute adverse effects were evaluated in the chimney, passive avoidance and grip-strength tests. Results. The three-drug mixture of OXC, PGB and TPM exerted supra-additive (synergistic) interaction in the mouse maximal electroshock-induced seizure model. The combination of OXC, PGB and TPM did not produce any acute adverse effects in mice in the chimney, passive avoidance and grip-strength tests. Conclusions. The isobolographic synergy observed experimentally for the combination of OXC, PGB and TPM could be recommended to patients with drug-resistant epilepsy, if the results of this study were translated to clinical settings.