RESEARCH PAPER
7-Nitroindazole does not affect the anti-convulsant action of gabapentin and tiagabine in pentylenetetrazole-induced seizures in mice
 
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1
Department of Pathophysiology, Medical University, Lublin, Poland
2
Department of Physiopathology, Institute of Agricultural Medicine, Lublin, Poland
3
First Department of Internal Medicine with Dialysis Station, County Hospital, Starachowice, Poland
4
Department of Neurology, Neuropsychiatric Hospital, Kielce, Poland
 
JPCCR 2007;1(2):150–154
KEYWORDS:
ABSTRACT:
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 (ED[sub]50 [/sub]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 ED[sub]50[/sub] values for GBP administered alone and in combination with 7-NI were 289 and 350 mg/kg. Similarly, the ED[sub]50[/sub] values for TGB administered alone and in combination with 7-NI were 0.7 and 0.8 mg/kg, respectively. Moreover, the examined combination of 7-NI (50 mg/kg) 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.
CORRESPONDING AUTHOR:
Jarogniew J. Łuszczki   
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland.
 
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