Comparative assessment of the anxiolytic-like activities of honokiol and derivatives

Honokiol has previously been shown to be an effective anxiolytic-like agent in mice when administered for 7 days at 0.2 mg/kg/day prior to evaluation in an elevated plus-maze, while 20 mg/kg is required for efficacy as a sing le oral dose. The aim of this study was to find analogs of honokiol that ar e more effective for acute administration. Among the eight analogs evaluate d, one partially reduced derivative of honokiol [3'-(2-propenyl)-5-propyl-( 1,1'-biphenyl)-2,4'-diol] exhibited significant anxiolytic-like activity at 0.04 mg/kg. Following oral administration of 1 mg/kg of this analog, anxio lytic-like activity was clearly evident at 1 h, peaked at 3 h, and remained significant for longer than 4 h after treatment. Combined administration o f the derivative with diazepam led to enhanced anxiolytic-like efficacy. Mo reover, as with diazepam, the anxiolytic-like effect of the analog was redu ced by flumazenil. In contrast, bicuculline, a GABA(A) antagonist, had no e ffect on the activity of the derivative. Taken together, these results sugg est that this analog of honokiol acts at the benzodiazepine recognition sit e of the GABA(A)-benzodiazepine receptor complex. (C) 2000 Elsevier Science Inc. All rights reserved.