INFLUENCE OF NITRIC OXIDE MODULATING AGENTS ON THE ANTICONVULSANT EFFECTS
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The precise role of NO in the expression of seizures is unclear. Some studies have revealed that NO synthetase (NOS) inhibitors, which block the formation of NO, can potentiate behavioral or electrographic effects of convulsant drugs suggesting that NO acts as an endogenous anticonvulsant. In contradiction to that, several other studies revealed that NO is proconvulsant. The present study is aimed to investigate the role of L-arginine : NO : cGMP pathway in antiepileptic activity of diazepam and clonazepam, the benzodiazepines commonly used in clinical practice as anticonvulsant. We used LNAME (NO synthetase inhibitor), L-arginine (substrate for NO formation) and methylene blue (guanyl cyclase inhibitor) in order to examine the possible involvement of NO in the anticonvulsant effects of benzodiazepines in the rat model of pilocarpine- induced convulsions. Our aim was to test if concomitant administration of these compounds, affecting the level of NO, with benzodiazepines results in synergy or antagonism of their anticonvulsant effects. The effect of diazepam (0.1 mg/ kg) and clonazepam (0.05 mg/kg) in reducing the number of animals developing convulsions, the frequency of seizure episodes and mortality rates was intensified by the NOS inhibitor, L-NAME (10 mg/kg). The above effect of L-NAME was reversed by L-arginine (250 mg/kg). The participation of NO: cGMP pathway in the anticonvulsant effects of benzodiazepines seems to be supported by intensification of these effects by methylene blue (5 mg/kg). The results of the present study indicate that NO may act as proconvulsant rather than anticonvulsant and it is involved in the anticonvulsant effects of benzodiazepines.