Accumulating experimental evidence indicates that nitric oxide (NO) plays an important role in the pathophysiology of seizures. The purpose of this study was to determine the effect of 7-nitroindazole (7-NI, a preferential neuronal nitric oxide synthase inhibitor) on the anticonvulsant activity of gabapentin (GBP) and tiagabine (TGB) – two newer antiepileptic drugs (AEDs) in the mouse pentylenetetrazole (PTZ)-induced seizure model. The clonic seizures in mice were evoked by subcutaneous injection of PTZ at a dose of 100 mg/kg. The clonic seizure activity was defined as clonus of the whole body lasting over 3 s, with an accompanying loss of righting reflex in mice. The anti-convulsant action of GBP and TGB against PTZ-induced seizures was expressed as median effective doses (ED50 values) of the AEDs, protecting 50% of animals tested against PTZ-induced seizures. The acute adverse-effect potentials of GBP and TGB in combination with 7-NI were evaluated by the chimney test (motor coordination). Results indicate that 7-NI administered intraperitoneally at a dose of 50 mg/kg did not significantly affect the anticonvulsant action of GBP and TGB against PTZ-induced seizures. The experimentally-derived ED50 values for GBP administered alone and in combination with 7-NI were 289 and 350 mg/kg. Similarly, the ED50 values for TGB administered alone and in combination with 7-NI were 0.7 and 0.8 mg/kg, respectively. Moreover, the with GBP (350 mg/kg) or TGB (0.8 mg/kg) did not affect motor coordination in the chimney test. In conclusion, 7-NI had no impact on the anti-convulsant activity of GBP and TGB in the mouse PTZ-induced seizure model, and did not affect motor coordination of mice challenged with the chimney test