Trivedi Madhukar H, Desaiah Durisala, Ossanna Melissa J, Pritchett Yili L, Brannan Stephen K, Detke Michael J
Mood Disorders Program and Clinic, University of Texas Southwestern Medical School, Dallas, TX 75235-9119, USA.
Int Clin Psychopharmacol. 2008 May;23(3):161-9. doi: 10.1097/YIC.0b013e3282f41d7e.
Most antidepressants in clinical use are believed to function by enhancing neurotransmission of serotonin [5-hydroxytryptamine (5-HT)] and/or norepinephrine (NE) via inhibition of neurotransmitter reuptake. Agents that affect reuptake of both 5-HT and NE (serotonin-norepinephrine reuptake inhibitors) have been postulated to offer greater efficacy for the treatment of major depressive disorder (MDD). These dual-acting agents also display a broader spectrum of action, including efficacy for MDD and associated painful physical symptoms, diabetic peripheral neuropathic pain, generalized anxiety disorder, and fibromyalgia syndrome. Substantial preclinical evidence shows that duloxetine, an approved drug for the treatment of MDD, generalized anxiety disorder, and the management of diabetic peripheral neuropathic pain, inhibits reuptake of both 5-HT and NE. This paper reviews clinical and neurochemical evidence of duloxetine's effects on 5-HT and NE reuptake inhibition. The clinical evidence supporting duloxetine's effects on NE reuptake inhibition includes indirect measures such as altered excretion of NE metabolites, cardiovascular effects, and treatment-emergent adverse event profiles similar to those for other drugs believed to act through the inhibition of NE reuptake. In summary, the data presented in this report provide clinical evidence of a mechanism for duloxetine involving both 5-HT and NE reuptake inhibition in humans and are consistent with preclinical evidence for 5-HT/NE reuptake inhibition.
目前临床使用的大多数抗抑郁药被认为是通过抑制神经递质再摄取来增强5-羟色胺（5-HT）和/或去甲肾上腺素（NE）的神经传递而发挥作用。据推测，影响5-HT和NE两者再摄取的药物（5-羟色胺-去甲肾上腺素再摄取抑制剂）对治疗重度抑郁症（MDD）具有更高的疗效。这些双效药物还具有更广泛的作用谱，包括对MDD及相关的疼痛性躯体症状、糖尿病性周围神经病变性疼痛、广泛性焦虑症和纤维肌痛综合征有效。大量临床前证据表明，度洛西汀（一种被批准用于治疗MDD、广泛性焦虑症和糖尿病性周围神经病变性疼痛的药物）可抑制5-HT和NE的再摄取。本文综述了度洛西汀对5-HT和NE再摄取抑制作用的临床及神经化学证据。支持度洛西汀对NE再摄取抑制作用的临床证据包括一些间接指标，如NE代谢产物排泄改变、心血管效应以及与其他据信通过抑制NE再摄取发挥作用的药物相似的治疗中出现的不良事件谱。总之，本报告中的数据提供了度洛西汀在人体内涉及5-HT和NE再摄取抑制机制的临床证据，并且与5-HT/NE再摄取抑制的临床前证据一致。
