Kuribara H, Kishi E, Kimura M, Weintraub S T, Maruyama Y
Department of Neuropsychopharmacology (Tsumura), Gunma University School of Medicine, 3-39-22 Showa-machi, Gunma 371-8511, Maebashi, Japan.
Pharmacol Biochem Behav. 2000 Nov;67(3):597-601. doi: 10.1016/s0091-3057(00)00401-9.
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 single oral dose. The aim of this study was to find analogs of honokiol that are more effective for acute administration. Among the eight analogs evaluated, 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, anxiolytic-like activity was clearly evident at 1 h, peaked at 3 h, and remained significant for longer than 4 h after treatment. Combined administration of the derivative with diazepam led to enhanced anxiolytic-like efficacy. Moreover, as with diazepam, the anxiolytic-like effect of the analog was reduced by flumazenil. In contrast, bicuculline, a GABA(A) antagonist, had no effect on the activity of the derivative. Taken together, these results suggest that this analog of honokiol acts at the benzodiazepine recognition site of the GABA(A)-benzodiazepine receptor complex.
厚朴酚此前已被证明，在高架十字迷宫试验前，以0.2毫克/千克/天的剂量给小鼠连续给药7天，它是一种有效的抗焦虑样药物，而单次口服给药的有效剂量为20毫克/千克。本研究的目的是寻找对急性给药更有效的厚朴酚类似物。在评估的8种类似物中，一种厚朴酚的部分还原衍生物[3'-(2-丙烯基)-5-丙基-(1,1'-联苯)-2,4'-二醇]在0.04毫克/千克时表现出显著的抗焦虑样活性。口服1毫克/千克这种类似物后，抗焦虑样活性在1小时时明显显现，3小时时达到峰值，给药后4小时以上仍保持显著。该衍生物与地西泮联合给药可增强抗焦虑样疗效。此外，与地西泮一样，氟马西尼可降低该类似物的抗焦虑样作用。相比之下，GABA(A)拮抗剂荷包牡丹碱对该衍生物的活性没有影响。综上所述，这些结果表明，这种厚朴酚类似物作用于GABA(A)-苯二氮䓬受体复合物的苯二氮䓬识别位点。
