Duloxetine pharmacology: profile of a dual monoamine modulator.
Duloxetine pharmacology: profile of a dual monoamine modulator.
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度洛西汀药理学：双重单胺调节剂的概况。
DOI：
10.1111/j.1527-3458.2002.tb00234.x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Lakoski,JoanM
中科院分区：
文献类型：
--
作者：
Karpa,KellyD;Cavanaugh,JaneE;Lakoski,JoanM
中枢单胺能系统失调被认为是抑郁症病理的基础。选择性抑制中枢单胺再摄取的药物已在临床上用于减轻抑郁症的症状。度洛西汀（Duloxetine）是目前正在研究的一种用于治疗抑郁症的新型化合物，它与去甲肾上腺素（NE）和血清素（5‐HT）转运体选择性结合，具有高亲和力，而与中枢神经系统内的单胺受体缺乏亲和力。有研究表明，单胺再摄取过程的双重抑制可能比目前使用的其他抗抑郁药更具优势。在临床前研究中，度洛西汀模拟了抗抑郁药的许多生理作用。与其他抗抑郁药一致，度洛西汀急性给药可提高细胞外单胺水平，而慢性给药不改变基础单胺水平。像选择性5 -羟色胺再摄取抑制剂氟西汀一样，通过微离子电泳应用，度洛西汀抑制神经元细胞放电。然而，与氟西汀相比，度洛西汀是一种更有效的血清素再摄取抑制剂。此外，在行为实验中，度洛西汀在抑郁症动物模型的强迫游泳试验中比其他几种常用的抗抑郁药更大程度地减弱了不动性。在一项为期六周的开放标签非对照研究中，对有抑郁症病史的患者使用度洛西汀进行了评估。度洛西汀治疗抑郁症有效，汉密尔顿抑郁评分显著降低。在度洛西汀治疗期间报告的不良反应是轻微的，与其他抗抑郁药相似。在一项为期8周的多中心、双盲、安慰剂对照研究中，在重度抑郁症患者中，度洛西汀作为抗抑郁药是有效的，特别是在症状严重的患者中。虽然有报道称度洛西汀的半衰期为10至15小时，但关于人体内度洛西汀的药代动力学数据有限。在健康受试者中进行的研究证实了度洛西汀作为5 -羟色胺和NE再摄取抑制剂的临床前特征。综上所述，现有数据表明度洛西汀是一种新型有效的抗抑郁药。
Dysregulation within central monoaminergic systems is believed to underlie the pathology of depression. Drugs that selectively inhibit the reuptake of central monoamines have been used clinically to alleviate symptoms of depressive illnesses. Duloxetine, a novel compound currently under investigation for the treatment of depression, binds selectively with high affinity to both norepinephrine (NE) and serotonin (5‐HT) transporters and lacks affinity for monoamine receptors within the central nervous system. It has been suggested that dual inhibition of monoamine reuptake processes may offer advantages over other antidepressants currently in use.In preclinical studies, duloxetine mimics many physiologic effects of antidepressants. Consistent with other antidepressants, duloxetine, by acute administration, elevates extracellular monoamine levels, while by chronic administration it does not alter basal monoamine levels. Like the selective serotonin reuptake inhibitor, fluoxetine, by microiontophoretic application, duloxetine inhibits neuronal cell firing. However, in comparison with fluoxetine, duloxetine is a more potent serotonin reuptake inhibitor. Furthermore, in behavioral experiments, duloxetine attenuates immobility in forced swim tests in animal models of depression to a greater extent than several other commonly used antidepressants.In a six‐week open label uncontrolled study, duloxetine was evaluated in patients with a history of depression. Duloxetine was effective in treating depression as determined by marked reduction in Hamilton Depression Rating scores. Adverse effects reported during duloxetine treatment were minor and similar to those of other antidepressants. In an eight‐week multicenter, double‐blind, placebo‐controlled study in patients with a major depressive disorder, duloxetine was effective as an antidepressant, particularly in patients with greater symptom severity. Only limited data are available regarding the pharmacokinetic profile of duloxetine in humans, although a half‐life of 10 to 15 h has been reported. Studies conducted in healthy human subjects confirm the preclinical profile of duloxetine as an inhibitor of 5‐HT and NE reuptake. Taken together, existing data suggest that duloxetine is a novel and effective antidepressant.