Interaction of tiagabine with valproate in the mouse pentylenetetrazole-induced seizure model: an isobolographic analysis for non-parallel dose-response relationship curves.

Purpose: To characterize the interaction between tiagabine (TGB) and valproate (VPA) -- two antiepileptic drugs in the mouse pentylenetetrazole (PTZ)-induced clonic seizure model, type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs) was used. Material and Methods: Clonic seizures were evoked in. albino Swiss mice by subcutaneous injection of PTZ at its CD97 (100 mg/kg). To ascertain the nature of interaction between TGB and VPA administered in combination, total brain concentrations if TGB and VPA were estimated bY using high-performance liquid chromatography (HPLC) and fluorescence polarization iimmunoassay (FPIA). Results: TGB and VPA produced clear-cut anticonvulsant effects against PTZ-induced clonic seizures in mice and their DRRCs were not parallel to one another. The type I isobolographic analysis for nonparallel DRRCs revealed that the combination of TGB with VPA at the fixed-ratio of 1 : 1 exerted additive interaction against PTZ-induced clonic seizures in mice. With FPIA, it was found that TGB did not affect-total brain VPA concentrations in experimental animals. Moreover, VPA had no significant impact on total brain Concentrations of TGB in mice, as measured with HPLC Conclusion: The additive interaction between TGB and VPA at the fixed-ratio of 1:1 in the mouse PTZ model was pharmacodynamic in nature. [ABSTRACT FROM AUTHOR]