7-Nitroindazole does not affect the anti-convulsant action of gabapentin and tiagabine in pentylenetetrazole-induced seizures in mice
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Department of Pathophysiology, Medical University, Lublin, Poland
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
First Department of Internal Medicine with Dialysis Station, County Hospital, Starachowice, Poland
Department of Neurology, Neuropsychiatric Hospital, Kielce, Poland
JPCCR 2007;1(2):150–154
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
Jarogniew J. Łuszczki   
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
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