Antagonism of the anxiolytic action of diazepam and chlordiazepoxide by the novel imidazopyridines, EMD 39593 and EMD 41717.
The imidazopyridines EMD 35993 and EMD 41717 antagonized the anticonflict actions of diazepam and chlordiazepoxide in rodent models which are predictive for anxiolytic action in man. In contrast to other described benzodiazepine antagonists, these compounds did not antagonize either the anticonvulsant or muscle relaxant properties of either benzodiazepine. Both EMD 39593 and EMD 41717 competitively inhibit the binding of [3H]diazepam to brain membranes, but do not exhibit regional differences in potency. These observations suggest that both EMD 39593 and EMD 41717 display some selectivity in antagonizing the anxiolytic properties of benzodiazepines, and as such may be useful tools in identifying neuronal substrates of anxiety.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D002243:Carbolines / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002707:Chlordiazepoxide / Q000037:antagonists & inhibitors*; D003975:Diazepam / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000927:Anticonvulsants; D002243:Carbolines; D007093:Imidazoles; D009125:Muscle Relaxants, Central; D001569:Benzodiazepines; D002707:Chlordiazepoxide; C024915:beta-carboline-3-carboxylic acid ethyl ester; C037594:EMD 39593; C037595:EMD 41717; D003975:Diazepam