杜金平+刘艳庭+武艺静+吴红华+徐砚通

[摘要] 现有抗抑郁药物临床起效缓慢，因此需要研发快速起效抗抑郁药物。植物挥发油显示具有快速起效抗抑郁潜能，首先，挥发油气味芳香能够直接刺激嗅神经，脂溶性高易于透过血脑屏障，挥发性强适合鼻腔脑靶向和吸入给药，能够快速调节脑功能，具有快速起效抗抑郁潜能；其次，抗抑郁活性植物挥发油化学和药理研究进展揭示了挥发油抗抑郁化学物质基础、抗抑郁效果及可能作用機制；再者，考察植物挥发油抗抑郁活性成分对快速起效抗抑郁靶点作用，发现植物挥发油化学成分能拮抗NMDA受体活性，提示植物挥发油具有快速起效抗抑郁靶点机制潜能；最后，探讨通过整合抗抑郁挥发油特性、快速起效抗抑郁靶点机制和给药方式，充分发挥植物挥发油快速起效抗抑郁优势，为新药研发提供方向。

[关键词] 植物； 挥发油； 快速； 抗抑郁

[Abstract] The existing antidepressants demonstrated delayed onset of clinical effects， so fast-onset antidepressants are required. Essential oil of herbs showed potentials fast-onset antidepressant potential. First， its aromatic odor can directly activate olfactory nerves； its high lipophilicity causes a high blood-brain barrier penetration rate； and its high volatility is suitable for nasal-brain targeting and inhalation delivery. Therefore， essential oils can rapidly regulate brain functions by multiple ways， suggesting a fast-onset antidepressant potential. Second， the advance of studies on chemistry and pharmacology of antidepressant essential oils demonstrated chemical substances， antidepressant effects and possible action mechanisms of antidepressant essential oils. Third， the effect of essential oils′ antidepressant components on fast-onset antidepressant targets was investigated. It was found that chemical constituents of essential oils antagonized NMDA receptor activities， suggesting that essential oils have fast-onset antidepressant effect. Finally， characteristics of essential oils， fast-onset antidepressant targets and drug delivery methods are integrated to give full play to essential oils′ fast-onset antidepressant advantage and provide a new direction for new drug discovery.

[Key words] herb； essential oil； fast-onset； antidepressant

现有抗抑郁药物临床起效缓慢，如三环类药物（TCAs）、单胺转运体抑制剂（MTIs）和单胺氧化酶抑制剂（MAOIs）等，需要持续给药至少3～6周时间，既影响患者治疗依从性，又不能及时控制重症抑郁症患者致残和自杀危险[1-2]，因此临床亟需快速起效抗抑郁药物。目前快速起效抗抑郁药物发现采用经典的药物靶点筛选方法，有别于传统抗抑郁药物靶点如单胺氧化酶（MAO）和单胺转运体（MTs），快速起效抗抑郁药物作用于新靶点，这些靶点根据起效时间可分为快速和中速两类，快速起效抗抑郁药物靶点为NMDA受体，起效时间在数小时内，代表性药物如氯胺酮；……