CGS 9896: A nonbenzodiazepine, nonsedating potential anxiolytic

Various behavioral and neurochemical studies indicate that CGS 9896 may represent a novel, nonsedating anxiolytic. This substance, chemically related to the benzodiazepine antagonist CGS 8216, was effective in conflict and nonconflict models of anxiety. At the same time, CGS 9896 did not disrupt rotorod performance or decrease levels of responding in various operant procedures. In fact, CGS 9896 reversed the deficit in rotorod behavior produced by diazepam. CGS 9896 did not generalize to diazepam in rats trained to discriminate diazepam from vehicle. However, rats trained to discriminate CGS 9896 from vehicle generalized classical benzodiazepines to CGS 9896. These results suggest an anxioselective effect associated with CGS 9896 discriminative stimuli. Preliminary studies suggest that this pyrazoloquinoline does not produce dependence. Neurochemical analysis reveals that CGS 9896 binds avidly to benzodiazepine receptors both in vitro and in vivo. However, the binding characteristics of this compound differ from classical benzodiazepines in various respects. Two alternative hypotheses are discussed that may explain the behavioral and neurochemical differences between CGS 9896 and classical benzodiazepines.