Dhawan Kamaldeep, Dhawan Sanju, Chhabra Sumit
Department of Drugs Control, Government of Haryana, Panchkula, India.
J Pharm Pharm Sci. 2003 May-Aug;6(2):215-22.
A tri-substituted benzoflavone moiety (BZF) recently isolated from the methanol extract of aerial parts of the plant Passiflora incarnata Linneaus had exhibited encouraging results in countering the dependence produced by addiction-prone substances like morphine, nicotine, cannabinoids and ethyl alcohol, during the studies performed by the authors. Since the BZF moiety had exhibited significant anxiolytic properties at 10 mg/kg p.o. dose in mice, therefore, it was desirable to evaluate this potential phyto-moiety (BZF) for its own dependence-liabilities It was also deemed viable to evaluate BZF moiety for its possible usefulness in countering the dependence-liabilities associated with the chronic use of benzodiazepines keeping in light their tremendous clinical use in the management of anxiety and insomnia.
Different groups of mice were administered BZF alone (10, 50 or 100 mg/kg, p.o.), and concomitantly with diazepam (20 mg/kg, p.o.) in a 21-days treatment regimen, followed by no treatments for the next 72-hours. The withdrawal effects in the form of ambulatory behavior of the treated animals were recorded on the 25th day using an Actophotometer.
The BZF-alone (three doses) treated mice exhibited a normal ambulatory behavior on 25th day. Mice groups receiving co-treatments, i.e., BZF-diazepam concomitantly, also exhibited a normal ambulatory behavior in a dose-dependent manner, i.e., the higher dose of BZF (100 mg/kg) being more effective in countering the withdrawal effects of chronically administered diazepam than the lower doses (10 or 50 mg/kg).
The studies revealed that the chronic administration of the BZF moiety (three doses), did not exhibit any dependence-liability of its own, even upon an abrupt cessation. Additionally, the BZF co-treatments with diazepam also prevented the incurrence of diazepam-dependence, which might be because of the aromatase enzyme inhibiting properties associated with the BZF moiety.
作者在研究过程中发现，最近从西番莲地上部分的甲醇提取物中分离出的三取代苯并黄酮部分（BZF），在对抗吗啡、尼古丁、大麻素和乙醇等易成瘾物质产生的依赖性方面显示出令人鼓舞的结果。由于BZF部分在小鼠口服剂量为10mg/kg时表现出显著的抗焦虑特性，因此，有必要评估这种潜在的植物部分（BZF）自身的依赖性倾向。鉴于苯二氮䓬类药物在治疗焦虑和失眠方面有大量临床应用，评估BZF部分在对抗与长期使用苯二氮䓬类药物相关的依赖性倾向方面的可能效用也被认为是可行的。
不同组的小鼠单独给予BZF（10、50或100mg/kg，口服），并在21天的治疗方案中与地西泮（20mg/kg，口服）同时给药，随后在接下来的72小时内不进行治疗。在第25天使用活动光度计记录治疗动物以行走行为形式表现出的戒断效应。
单独给予BZF（三个剂量）治疗的小鼠在第25天表现出正常的行走行为。同时接受联合治疗（即BZF - 地西泮）的小鼠组也以剂量依赖性方式表现出正常的行走行为，即较高剂量的BZF（100mg/kg）比较低剂量（10或50mg/kg）更有效地对抗长期给予地西泮的戒断效应。
研究表明，长期给予BZF部分（三个剂量），即使突然停药，也未表现出自身的任何依赖性倾向。此外，BZF与地西泮的联合治疗也预防了地西泮依赖性的发生，这可能是由于BZF部分具有芳香化酶抑制特性。
