Additive interactions of pregabalin with lamotrigine, oxcarbazepine and topiramate in the mouse maximal electroshock-induced seizure model: A type I isobolographic analysis for non-parallel dose–response relationship curves

Abstract

The aim of this study was to characterize the anticonvulsant effects of pregabalin (PGB-a third-generation antiepileptic drug) in combination with three second-generation antiepileptic drugs (i.e., lamotrigine [LTG], oxcarbazepine [OXC] and topiramate [TPM]) in the mouse maximal electroshock (MES)-induced seizure model by using the type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs). Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25mA, 500V, 50Hz, 0.2s stimulus duration) delivered via auricular electrodes. Potential adverse-effect profiles of interactions of PGB with LTG, OXC and TPM at the fixed-ratio of 1:1 in the MES test with respect to motor performance, long-term memory and skeletal muscular strength were measured. In the mouse MES model, PGB administered singly had its DRRC non-parallel to that for LTG, OXC and TPM. With type I isobolography for non-parallel DRRCs, the combinations of PGB with LTG, OXC and TPM at the fixed-ratio of 1:1 exerted additive interaction. In all combinations, neither motor coordination, long-term memory nor muscular strength were affected. In conclusion, the additive interactions between PGB and LTG, OXC and TPM are worthy of consideration while extrapolating the results from this study to clinical settings.