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(L.)Dunal 的生物活性化合物二十二烷醇阿魏酸酯具有很强的抗焦虑特性,但没有典型的苯二氮䓬类副作用。

The biologically active compound of (L.) Dunal, docosanyl ferulate, is endowed with potent anxiolytic properties but devoid of typical benzodiazepine-like side effects.

机构信息

Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.

Institute of Neuroscience, National Research Council (C.N.R.), University Campus, Cagliari, Italy.

出版信息

J Psychopharmacol. 2021 Oct;35(10):1277-1284. doi: 10.1177/02698811211008588. Epub 2021 May 3.

DOI:10.1177/02698811211008588
PMID:33934670
Abstract

BACKGROUND

Clinical and experimental studies support the therapeutic potential of () (L.) Dunal on anxiety disorders. This potential is attributable to components present in different plant extracts; however, the individual compound(s) endowed with specific anxiolytic effects and potential modulatory activity of the GABA receptor complex (GABAR) have remained unidentified until the recent isolation from a WS methanolic root extract of some GABAR-active compounds, including the long alkyl-chain ferulic acid ester, docosanyl ferulate (DF).

AIMS

This study was designed to assess whether DF (0.05, 0.25 and 2 mg/kg), similarly to diazepam (2 mg/kg), may exert anxiolytic effects, whether these effects may be significantly blocked by the benzodiazepine antagonist flumazenil (10 mg/kg) and whether DF may lack some of the benzodiazepines' typical motor, cognitive and motivational side effects.

METHODS

The behavioural paradigms Elevated Plus Maze, Static Rods, Novel Object Recognition, Place Conditioning and potentiation of ethanol-induced Loss of Righting Reflex were applied on male CD-1 mice.

RESULTS

Similarly to diazepam, DF exerts anxiolytic effects that are blocked by flumazenil. Moreover, at the full anxiolytic dose of 2 mg/kg, DF lacks typical benzodiazepine-like side effects on motor and cognitive performances and on place conditioning. Moreover, DF fails to potentiate ethanol's (3 g/kg) depressant activity at the ethanol-induced Loss of Righting Reflex paradigm.

CONCLUSIONS

These data point to DF as an effective benzodiazepine-like anxiolytic compound that, in light of its lack of motor, mnemonic and motivational side effects, could be a suitable candidate for the treatment of anxiety disorders.

摘要

背景

临床和实验研究支持()(L.)Dunal 对焦虑症的治疗潜力。这种潜力归因于不同植物提取物中存在的成分;然而,直到最近从 WS 甲醇根提取物中分离出一些 GABA 受体复合物(GABAR)活性化合物,包括长链烷基咖啡酸酯二十二烷酯(DF),才确定了具有特定抗焦虑作用和潜在调节 GABA 受体复合物(GABAR)活性的单一化合物。

目的

本研究旨在评估 DF(0.05、0.25 和 2mg/kg)是否与地西泮(2mg/kg)相似,具有抗焦虑作用,这些作用是否可被苯二氮䓬拮抗剂氟马西尼(10mg/kg)显著阻断,以及 DF 是否可能缺乏一些苯二氮䓬的典型运动、认知和动机副作用。

方法

采用高架十字迷宫、静态棒、新物体识别、位置条件和乙醇诱导的翻正反射丧失的增强等行为范式,对雄性 CD-1 小鼠进行测试。

结果

与地西泮相似,DF 具有抗焦虑作用,可被氟马西尼阻断。此外,在完全抗焦虑剂量 2mg/kg 时,DF 缺乏典型的苯二氮䓬样副作用,对运动和认知表现以及位置条件无影响。此外,DF 未能增强乙醇(3g/kg)在乙醇诱导的翻正反射丧失模型中的抑制活性。

结论

这些数据表明 DF 是一种有效的苯二氮䓬样抗焦虑化合物,由于缺乏运动、记忆和动机副作用,它可能是治疗焦虑症的合适候选药物。

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