Kuribara H, Stavinoha W B, Maruyama Y
Department of Neurobiology and Behaviour, Behaviour Research Institute, Gunma University School of Medicine, Maebashi, Japan.
J Pharm Pharmacol. 1998 Jul;50(7):819-26. doi: 10.1111/j.2042-7158.1998.tb07146.x.
Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. We have investigated the characteristics of the behavioural effects of honokiol by means of an elevated plus-maze test. In the plus-maze test a single oral dose of 20 mg kg(-1) honokiol significantly prolonged the time spent in the open arms of the maze, suggesting anxiolytic effect. Moreover, when honokiol was administered daily for seven days and the plus-maze test was conducted 3 or 24 h after the last administration, significant prolongation of the time in the open arms was manifested even for doses of 0.2 mg kg(-1). The maximum effect was observed for doses of 0.5 mg kg(-1). Honokiol at any dose in both single and repeated administration schedules caused neither change in motor activity nor disruption of traction performance. Orally administered diazepam, 0.5-2 mg kg(-1), caused dose-dependent prolongation of the time spent in the open arms of the maze with a significant increase in motor activity at 1 mg kg(-1), and dose-dependent disruption of traction performance. The changes in the plus-maze performance after treatment for seven days with 0.2 mg kg(-1) honokiol and after a single treatment with 1 mg kg(-1) diazepam were almost equivalent. The effect of honokiol (0.2 mg kg(-1), treatment for seven days) was inhibited by subcutaneous flumazenil (0.3 mg kg(-1)) and (+)-bicuculline (0.1 mg kg(-1)) and by intraperitoneal CCK-4 (50 microg kg(-1)) and caffeine (30 mg kg(-1)). The anxiolytic effect of diazepam (1 mg kg(-1)) was also inhibited by flumazenil and bicuculline. However, the combined administration of diazepam with caffeine enhanced the effect, and diazepam completely reversed the effect of CCK-4. These results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or disinhibition. The combined effects of the drug also revealed that the mechanism of anxiolytic effect of honokiol is partially different from that of diazepam.
厚朴酚是厚朴树皮中的一种新木脂素衍生物，具有中枢抑制作用，且在低得多的剂量下具有抗焦虑活性。我们通过高架十字迷宫试验研究了厚朴酚行为效应的特征。在十字迷宫试验中，单次口服20 mg·kg⁻¹厚朴酚可显著延长在迷宫开放臂停留的时间，提示具有抗焦虑作用。此外，当厚朴酚连续7天每日给药，并在末次给药后3或24小时进行十字迷宫试验时，即使剂量为0.2 mg·kg⁻¹，在开放臂停留的时间也显著延长。在剂量为0.5 mg·kg⁻¹时观察到最大效应。单次和重复给药方案中，任何剂量的厚朴酚均未引起运动活动的改变或牵引性能的破坏。口服0.5 - 2 mg·kg⁻¹地西泮可引起剂量依赖性地延长在迷宫开放臂停留的时间，在1 mg·kg⁻¹时运动活动显著增加，且剂量依赖性地破坏牵引性能。用0.2 mg·kg⁻¹厚朴酚治疗7天和单次用1 mg·kg⁻¹地西泮治疗后，十字迷宫试验表现的变化几乎相当。厚朴酚（0.2 mg·kg⁻¹，治疗7天）的作用被皮下注射氟马西尼（0.3 mg·kg⁻¹）、（+） - 荷包牡丹碱（0.1 mg·kg⁻¹）、腹腔注射CCK - 4（50 μg·kg⁻¹）和咖啡因（30 mg·kg⁻¹）抑制。地西泮（1 mg·kg⁻¹）的抗焦虑作用也被氟马西尼和荷包牡丹碱抑制。然而，地西泮与咖啡因联合给药增强了效应，且地西泮完全逆转了CCK - 4的效应。这些结果表明，与地西泮不同，厚朴酚选择性地诱导抗焦虑作用，引发运动功能障碍、镇静或去抑制的可能性较小。药物的联合效应还表明，厚朴酚抗焦虑作用的机制与地西泮部分不同。
