Triazolobenzodiazepines antagonize the effects of anxiogenic drugs mediated at three different central nervous system sites.

The ability of the triazolobenzodiazepines to antagonize the anxiogenic effects of three different compounds in the social interaction test was investigated. The compounds were selected for their different sites of action in the central nervous system: FG 7142, acting at the beta-carboline site on the gamma-aminobutyric acid-benzodiazepine receptor complex; pentylenetetrazole, acting at the picrotoxin site on this complex, and yohimbine, an alpha 2-adrenoceptor antagonist. Adinazolam (5 mg/kg) and U-43,465 (32 mg/kg) were able to antagonize the anxiogenic effects of all three compounds, unlike classical 1,4-benzodiazepines, that are not able to antagonize the effects of yohimbine. The results are discussed in terms of the anti-panic activity of the triazolobenzodiazepines.