title: RO 15-1788 selectively reverses antagonism of pentylenetetrazol-induced discriminative stimuli by benzodiazepines but not by barbiturates.
abstract: The specificity of ethyl 8-fluro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo (1,5-a) (1,4) benzodiazepine-3-carboxylate (RO 15-1788) in reversing the effectiveness of diazepam and des-methylclobazam, but not of pentobarbital, in antagonizing discriminative stimuli produced by pentylenetetrazol is described. Male hooded rats were trained to discriminate pentylenetetrazol-induced interoceptive discriminative-stimuli (IDS) in a two-lever choice paradigm on an FR10 schedule of food reinforcement. These IDS pharmacologically model verbal report of anxiogenic activity in humans. Diazepam (1,4 benzodiazepine), des-methylclobazam (1,5 benzo-diazepine), and pentobarbital antagonized pentylenetetrazol-IDS. RO 15-1788 neither generalized to nor antagonized pentylenetetrazol-IDS. It also did not cause convulsions in pentylenetetrazol sensitized rats at doses up to 40 mg/kg. It did, however, antagonize the action of diazepam (10 mg/kg) as well as that of des-methylclobazam (160 mg/kg) but not that of pentobarbital. These data suggest that RO 15-1788 is not an anxiomimetic, anxiolytic or a convulsant drug, but it is a specific and effective antagonist of anxiolytic action of benzodiazepines.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors*; D000927:Anticonvulsants / Q000037:antagonists & inhibitors*; D001463:Barbiturates / Q000037:antagonists & inhibitors*; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003975:Diazepam / Q000037:antagonists & inhibitors; D005442:Flumazenil; D008297:Male; D010424:Pentobarbital / Q000037:antagonists & inhibitors; D010433:Pentylenetetrazole / Q000494:pharmacology*; D051381:Rats; D013268:Stimulation, Chemical
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001463:Barbiturates; D001570:Benzodiazepinones; D001569:Benzodiazepines; D005442:Flumazenil; D010424:Pentobarbital; C024581:N-desmethylclobazam; D003975:Diazepam; D010433:Pentylenetetrazole