Interactions between oxcarbazepine and conventional antiepileptic drugs in the maximal electroshock test in mice: An isobolographic analysis

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.