Summary:  Purpose: The aim of this study was to determine the types of interactions between oxcarbazepine (OCBZ) and conventional antiepileptic drugs (AEDs) against maximal electroshock‐induced seizures (MES test) in mice, by using a method of isobolographic analysis.Methods: Adverse effects of combinations were evaluated in the chimney test (motor performance), also using the isobolographic method, which allowed determination of the median toxic dose (TD₅₀) values for individual combinations; thus the protective indices could be determined.Results: OCBZ and phenytoin (PHT) at the fixed‐ratio combination of 1:1 were significantly infraadditive (antagonistic) with respect to the antiseizure protection against MES and simultaneously additive in terms of side effects in the chimney test. Interestingly, combinations between OCBZ and clonazepam (CZP) in the MES test proved antagonistic or synergistic, depending on the proportion of both AEDs in the mixture. Low doses of OCBZ with high doses of CZP exerted antagonism. Conversely, high doses of OCBZ combined with low doses of CZP resulted in a synergistic interaction. Remaining combinations between OCBZ and phenobarbital, valproate, or carbamazepine were purely additive, either as regards the anticonvulsant activity against MES or in terms of motor impairment in the chimney test.Conclusions: The results of this study indicate that interaction of OCBZ and CZP at fixed‐ratio combination of 1:1 might be profitable from a clinical point of view. Conversely, combinations of OCBZ with PHT may not be clinically efficient.

Summary:  Purpose: The objective of this study was the isobolographic evaluation of the interactions between the novel antiepileptic drug (AED) gabapentin (GBP) and a number of other AEDs against electroconvulsion‐induced convulsions in mice.Methods: Electroconvulsions were produced by means of an alternating current (ear‐clip electrodes, 0.2‐s stimulus duration, tonic hindlimb extension taken as the end point). Adverse effects were evaluated with the chimney test (motor performance) and passive‐avoidance task (long‐term memory). Plasma levels of AEDs were measured by immunofluorescence or high‐pressure liquid chromatography.Results: GBP (≤50 mg/kg) remained ineffective on the electroconvulsive threshold. According to the isobolographic analysis, GBP appears to act synergistically with carbamazepine, valproate, phenytoin, phenobarbital (PB), lamotrigine (LTG), and LY 300164. The pharmacokinetic events may be responsible for the interactions of GBP/PB and GBP/LTG, because only PB and LTG significantly elevated the plasma concentration of this AED. Conversely, GBP did not affect the plasma levels of other AEDs used in this study. No adverse effects were induced by combinations of GBP with these AEDs.Conclusions: The isobolographic analysis revealed that combinations of GBP with other AEDs generally results in synergistic (supraadditive) interactions.

Summary:  Purpose: The study investigated the types of interactions between lamotrigine (LTG) and first‐generation antiepileptic drugs (AEDs) or topiramate (TPM) with isobolographic analysis. Methods: Anticonvulsant and adverse‐effect profiles of combinations of LTG with other AEDs, at fixed ratios of 1:3, 1:1, and 3:1, were evaluated in the maximal electroshock (MES)‐induced seizures and the chimney test (motor performance) in mice, which allowed the determination of benefit indices (BIs) for individual combinations. Results: Combinations of LTG with TPM or valproate (VPA), at fixed ratios of 1:1, were significantly supraadditive (synergistic) in the MES test and, simultaneously, subadditive (antagonistic) in the chimney test, showing the best profile for AED combinations. In contrast, combinations between LTG and carbamazepine (CBZ), in terms of antiseizure protection against MES, were subadditive (antagonistic) and additive in the chimney test, resulting in unfavorable AED combinations. Moreover, the combination of LTG with phenobarbital (PB), at a fixed ratio of 1:1, despite synergy in the MES test, also was synergistic in the chimney test, resulting in a modest BI for AED combination. LTG combined with phenytoin was additive in both the MES and chimney tests in mice. The remaining combinations, at fixed ratios not mentioned earlier, also showed an average BI for AED combinations. Furthermore, LTG combined with all studied AEDs did not affect long‐term memory in mice. None of the AEDs influenced the free plasma level of LTG, whereas LTG slightly reduced the free plasma concentration of PB. Conclusions: Interactions between LTG and TPM or LTG and VPA at a fixed ratio of 1:1 might be profitable from a preclinical point of view, displaying the most optimal BI.