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. |
