单萜(-)-冰片对小鼠的抗焦虑/镇静作用及其与GABAA受体的硅分子相互作用

Maurício P. M. Amaral, Marcelo Pereira da Silva Junior, Francisco das Chagas Alves Lima, S. Gutierrez, D. Arcanjo, R. C. M. Oliveira
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引用次数: 3

摘要

焦虑是一种正常的行为。当它太频繁或出现在不适当的语境中,它可以被认为是病态的。苯二氮卓类药物(BDZs)是临床成功治疗焦虑的药物。BDZs作为γ-氨基丁酸A受体(GABAAR)的变构调节剂。然而,这些药物会产生副作用。尽管BDZs在治疗方面取得了进展,但对不良反应较少的抗焦虑药的研究仍在继续。单萜(-)-冰片[(-)-bor]的研究证明了其药理学特性,如GABAAR的部分激动剂作用和抗惊厥作用。另一方面,没有工作已开发评估抗焦虑/镇静的潜力。本研究的目的是研究(-)- bor在25、50和100 mg/kg (i.p.)剂量下对动物模型的抗焦虑/镇静作用,以及是否与GABAAR存在分子相互作用。单萜(-)- bor对瑞士小鼠(25-30 g)采用升高+迷宫法、开场法和光暗箱法三种焦虑模型进行抗焦虑作用试验。硫喷妥诱导的睡眠时间模型是一种与GABAARs相关的镇静和催眠活动的药物筛选。在分子对接中,使用AutoDock 4.2.6程序进行GABAAR分子与(-)- bor的相互作用。结果表明(-)- bor具有镇静和抗焦虑活性。分子对接研究表明(-)- bor可以通过氢键与GABAARs相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anxiolytic/Sedative Effect of Monoterpene (–)-Borneol in Mice and In Silico Molecular Interaction with GABAA Receptor
Anxiety is a normal behavioral component. When it is too frequent or appears in inappropriate contexts, it can be considered pathological. Benzodiazepines (BDZs) are drugs with clinical success in anxiety treatment. BDZs act as allosteric modulators of the γ- aminobutyric acid A receptor (GABAAR). However, these drugs cause adverse effects. Despite the therapeutic advances obtained with BDZs, the search for anxiolytics with fewer adverse effects is ongoing. Studies with monoterpene (–)-borneol [(–)-BOR] demonstrated pharmacological properties such as a partial agonist effect of GABAAR and an anticonvulsive effect. On the other hand, no work has been developed evaluating the anxiolytic/sedative potential. The objective of this study was to investigate the anxiolytic/sedative effects of (–)-BOR in animal models at doses of 25, 50, and 100 mg/kg (i.p.) and whether there was a molecular interaction with GABAAR. The anxiolytic effect of monoterpene (–)-BOR was tested on Swiss mice (25–30 g) in three anxiety models: the elevated plus maze test, the open field test, and the light-dark box test. The thiopental-induced sleep time model was a drug screen for the sedative and hypnotic activity related to GABAARs. In the molecular docking, the interaction between the GABAAR molecule and (–)-BOR was performed using the AutoDock 4.2.6 program. The results demonstrated that (–)-BOR has sedative and anxiolytic activity. The molecular docking study revealed that (–)-BOR can interact with GABAARs through hydrogen bonds.
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