No eff ect of 7-nitroindazole on the anticonvulsant action of vigabatrin and oxcarbazepine in pentylenetetrazole-induced seizures in mice

The aim of this study was to determine the eff ect of 7-nitroindazole (7-NI – a preferential neuronal nitric oxide synthase inhibitor) on the protective action of oxcarbazepine (OXC) and vigabatrin (VGB) – two newer antiepileptic drugs (AEDs) against pentylenetetrazole (PTZ)-induced seizures in mice. The clonic seizure activity in mice was evoked by subcutaneous injection of PTZ (100 mg/kg) and defi ned as clonus of the whole body lasting over 3 s with an accompanying loss of righting refl ex in mice. The protective action of OXC and VGB against PTZ-induced clonic seizures was expressed as their median eff ective doses (ED50 values) suppressing clonic seizures in 50% of animals tested. The acute adverse-eff ect potentials of OXC and VGB in combination with 7-NI were evaluated in the chimney test (motor coordination) in mice. Results indicate that 7-NI administered intraperitoneally (50 mg/kg) did not signifi cantly aff ect the anticonvulsant action of OXC or VGB against PTZ-induced clonic seizures. The ED50 values for OXC administered alone and in combination with 7-NI were 20.9 and 24.8 mg/kg. Similarly, the ED50 values for VGB administered alone and in combination with 7-NI were 595 and 622 mg/kg, respectively. Moreover, the examined combinations of 7-NI (50 mg/kg) with OXC (24.8 mg/kg) and VGB (622 mg/kg) did not aff ect motor coordination in the chimney test. In conclusion, 7-NI had no signifi cant impact on the anticonvulsant activity of OXC and VGB in the mouse PTZ-induced seizure model, and did not aff ect motor coordination in animals subjected to the chimney