The reversal of
anticonvulsant effect of
ethanol against chemoconvulsions by
RO15-4513 was investigated in rats as this novel imidazobenzodiazepine (ethyl-8 azido-5, 6-dihydro-5-methyl-6-Oxo-4H-imidazo [1,5a] [1,4]
benzodiazepine-3-carboxylate) is reported to antagonize the acute behavioral and biochemical effects of
ethanol in animals. Reversal of
ethanol effects on onset of
myoclonic jerks, tonic extensor phase, mortality time and percent protection against mortality were compared with not only other
anticonvulsant pentobarbital but also with another inverse agonist
FG-7142. Pretreatment with
RO15-4513 (4 mg/kg) reversed the protective effect of
ethanol against
bicuculline-induced tonic extensor phase and mortality (87%). This response was sensitive to reversal by RO15-1788 (10 mg/kg). However, onset of
myoclonic jerks and duration of clonus were not significantly altered. It also reversed the effect against
picrotoxin but the reversal against mortality was up to 50%. As compared to
ethanol,
RO15-4513 reversed partially the protective effect of
pentobarbital against
bicuculline- and
picrotoxin-induced convulsions.
FG-7142 failed to reverse the protective effect of
ethanol and
pentobarbital against
bicuculline-induced tonic extensor phase although it reversed the effect against onset and mortality. It had no effect on the protective effect against
picrotoxin-induced convulsions. Both
RO15-4513 and
FG-7142 possessed proconvulsant effects against
bicuculline but not against
picrotoxin. These observations suggest that
RO15-4513 has a more preferential action against
ethanol effects as compared to the other inverse agonist.