Interaction of pregabalin with valproate in the mouse maximal electroshock-induced seizure model: an isobolographic analysis
DOI:
https://doi.org/10.12923/Keywords:
Pregabalin, valproate, isobolographic analysis, maximal electroshock, pharmacodynamic/pharmacokinetic interactionAbstract
The aim of this study was to characterize the interaction between pregabalin (PGB – a third-generation antiepileptic drug) and valproate (VPA – a classical antiepileptic drug) in the maximal electroshock (MES)-induced seizure model in mice 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 (25mA, 500V, 50Hz, 0.2s stimulus duration) delivered via auricular electrodes. In the mouse MES model, PGB administered singly had its DRRC non-parallel to that for VPA. According to type I isobolographic analysis for non-parallel DRRCs, the combination of PGB with VPA at the fixed-ratio of 1:1 exerted additive interaction. Pharmacokinetic studies revealed that PGB had no impact on total brain concentrations of VPA in experimental animals. Moreover, PGB, VPA and their combination at the fixed-ratio of 1:1 did not alter motor performance, long-term memory or skeletal muscular strength in experimental animals. In conclusion, the additive interaction between PGB and VPA is worthy of consideration while extrapolating the results from this preclinical study to clinical settings.
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