Effect of N(G)-nitro-L-arginine on the anticonvulsant action of four second-generation antiepileptic drugs in pentetrazole-induced clonic seizures in mice.
Journal Title: Pharmacological Reports - Year 2007, Vol 59, Issue 4
Abstract
The exact role of compounds modulating nitric oxide (NO) content in the brain during seizure phenomena is under intensive investigation. This study was aimed at determining the effect of N(G)-nitro-L-arginine (L-NA; a non-selective NO synthase inhibitor) on the anticonvulsant activity of four second-generation antiepileptic drugs (AEDs: gabapentin [GBP], oxcarbazepine [OXC], tiagabine [TGB] and vigabatrin [VGB]) in the mouse pentetrazole (PTZ)-induced seizure model. The acute adverse-effect liability of the studied AEDs in combinations with L-NA were evaluated in the chimney test (motor coordination). Results indicate that L-NA (40 mg/kg; ip) significantly reduced the anticonvulsant activity of OXC in the PTZ test, by increasing its ED(50) from 20.9 to 29.8 mg/kg (p < 0.05). Similarly, L-NAat doses of 20 and 40 mg/kg considerably attenuated the antiseizure effects of VGB by raising its ED(50) from 595 to 930 mg/kg (p < 0.05), and 1022 mg/kg (p < 0.01), respectively. L-NA at lower doses of 10 and 20 mg/kg did not affect significantly the anticonvulsant effects of VGB and OXC in PTZ-induced seizures. Likewise, the co-administration of L-NA(40 mg/kg; ip) with GBPand TGB was associated with no significant changes in their anticonvulsant activities in PTZ-induced seizures in mice. Moreover, none of the examined combinations of L-NA (40 mg/kg; ip) and second-generation AEDs (at their ED(50) values) affected motor coordination in the chimney test. Based on this preclinical study, one can conclude that L-NA reduced the anticonvulsant activities of VGB and OXC in the mouse PTZ-induced seizure model. Only, GBP and TGB were resistant to the action of L-NA in this model.
Authors and Affiliations
Jarogniew Łuszczki, Marcin Szadkowski, Stanisław Czuczwar
Keywords
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