CGS 9896: A nonbenzodiazepine, nonsedating potential anxiolytic

Abstract

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.

Pharmacologic characterization of a novel non-benzodiazepine selective anxiolytic, DN-2327.

“…Wood et al (19) reported that the non sedating benzodiazepine agonist/antagonist CGS9896 had a GABA ratio of 1 (24) exert an agonistic action on one class of benzodiazepine receptors and an antagonistic action on another class. It has been suggested that these compounds have affinities for the benzodiazepine receptors of the cerebellum that are different from those for the cerebral cortex receptors and that they have good separation ratios between their anxiolytic action and side effects.…”

Evaluation of the anticonvulsant and biochemical activity of CGS 8216 and CGS 9896 in animal models

“…CGS8216 blocks the anticonvulsant effects of CGS9896 (Bennett and Petrack, 1984). In our experiments, it completely and rapidly antagonized the suppressant action of CGS 9896 on absence-like seizures, and its effect was more persistent than that of Ro 15-1788 on the anti-petit mal effect of diazepam.…”

Yohimbine‐induced seizures in mice: A model predictive of potential anxiolytic and GABA‐mimetic agents

“…This is similar to the rank order of potency of these compounds in the yohimbine-induced seizure model. Similarly, the nonbenzodiazepine anxiolytics, namely, CGS 9896, CL 218,872, zopiclone, and tracazolate have been shown to interact with the benzodiazepine-GABA receptor complex [Olsen, 19811 and have all shown anxiolytic properties as anticonvulsants and in conflict models [Lippa et al, 1979a;Patel and Malick, 1982;Bernard et al, 1983Bernard et al, , 1985Goldberg et al, 1983;Julou et al, 1983Julou et al, , 1985Bennett and Petrack, 1984;Malick et al, 1984;Patel et al, 19851. However, CGS 9896 has shown weak anticonvulsant activity in mice in the pentylenetetrazol [Brown et al, 19841 and picrotoxin assays [Pellow, 19851.…”