Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba, 58051-085, Via Ipê Amarelo, S/N, João Pessoa, Paraíba, Brazil.
Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba, 58051-900, Via Ipê Amarelo, S/N, João Pessoa, Paraíba, Brazil.
Curr Top Med Chem. 2022;22(18):1530-1552. doi: 10.2174/1568026622666220505104726.
Although drugs currently available for the treatment of anxiety and depression act through modulation of the neurotransmission systems involved in the neurobiology of the disorder, yet they often present side effects, which can impair patient adherence to treatment.
This has driven the search for new molecules with anxiolytic and antidepressant potential. Aromatic plants are rich in essential oils, and their chemical constituents, such as monoterpenes, are being studied for these disorders. This study aims to evaluate the anxiolytic and antidepressant-like potential of the monoterpene tetrahydrolinalool in in vivo animal models and review pharmacological targets with validation through molecular docking. Male Swiss mice (Mus musculus) were treated with THL (37.5-600 mg kg p.o.) and submitted to the elevated plus maze, open field, rotarod, and forced swim tests. In the elevated plus-maze, THL at doses of 37.5 and 75 mg kg induced a significant increase in the percentage of entries (72.7 and 64.3% respectively), and lengths of stay (80.3 and 76.8% respectively) in the open arms tests.
These doses did not compromise locomotor activity or motor coordination in the animals. In the open field, rotarod tests, and the forced swimming model, treatment with THL significantly reduced immobility times at doses of 150, 300, and 600 mg kg, and by respective percentages of 69.3, 60.9 and 68.7%.
In molecular docking assay, which investigated potential targets, THL presented satisfactory energy values for: nNOs, SGC, IL-6, 5-HT1A, NMDAr, and D1. These demonstrate the potential of THL (a derivative of natural origin) in in vivo and in silico models, making it a drug candidate.
尽管目前用于治疗焦虑和抑郁的药物通过调节与疾病神经生物学相关的神经递质系统起作用，但它们常常存在副作用，这可能会影响患者对治疗的依从性。
这促使人们寻找具有抗焦虑和抗抑郁潜力的新分子。芳香植物富含精油，其化学成分，如单萜烯，正在针对这些疾病进行研究。本研究旨在评估单萜四氢芳樟醇（THL）在体内动物模型中的抗焦虑和抗抑郁样作用，并通过分子对接验证其药理学靶点。雄性瑞士小鼠（Mus musculus）用 THL（37.5-600mg/kg 口服）处理，并进行高架十字迷宫、旷场、转棒和强迫游泳测试。在高架十字迷宫中，THL 剂量为 37.5 和 75mg/kg 时，分别显著增加了进入开放臂的次数（分别为 72.7%和 64.3%）和停留时间（分别为 80.3%和 76.8%）。
这些剂量不会影响动物的运动活性或运动协调性。在旷场、转棒和强迫游泳模型中，THL 治疗剂量为 150、300 和 600mg/kg 时，显著减少了不动时间，分别减少了 69.3%、60.9%和 68.7%。
在潜在靶点的分子对接试验中，THL 对 nNOs、SGC、IL-6、5-HT1A、NMDAr 和 D1 表现出令人满意的能量值。这些结果表明 THL（一种天然来源的衍生物）在体内和计算机模型中具有潜力，使其成为一种候选药物。
