CGS 8216 and CGS 9896, novel pyrazoloquinoline benzodiazepine ligands with benzodiazepine agonist and antagonist properties.

CGS 8216 and CGS 9896 are two recently described compounds which interact with benzodiazepine binding sites but have pharmacological, biochemical and behavioral characteristics which distinguish them from classical benzodiazepines. CGS 8216 shows properties of a weak inverse agonist, while CGS 9896 shows properties of a mixed agonist/antagonist. Experiments using quantitative autoradiography to determine benzodiazepine binding site interactions of these compounds in discrete anatomical areas are described. Results indicate that [3H]-CGS 8216 does not show any regional differentiation in binding characteristics in 7 brain areas studied. CGS 9896 preferentially inhibited [3H]-flunitrazepam from cerebellar sites compared to hippocampal dentate gyrus sites, but the magnitude of this effect was small. These data support the conclusion that CGS 9896 is acting preferentially at putative benzodiazepine type 1 sites and is consistent with the mixed agonist/antagonist profile of the compound.