Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside.
Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: evidence from the bench and the bedside.
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DOI：
10.1016/j.pharmthera.2012.08.013
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发表时间：
2012-12
影响因子：
13.5
通讯作者：
Napier, T. Celeste
中科院分区：
文献类型：
--
作者：
Graves, Steven M.;Rafeyan, Roueen;Watts, Jeffrey;Napier, T. Celeste
关键词：
近年来，对物质使用障碍（SUD）和与禁欲相关的问题的理解有所增加。尽管如此，针对复发预防的高效治疗仍然难以捉摸，并且仍然没有FDA批准的用于精神兴奋剂依赖的药物疗法。临床前和临床研究评估的经典抗抑郁药，阻止单胺再摄取的效用，显示混合，往往是矛盾的结果。米氮平（Remeron®）是一种独特的FDA批准的抗抑郁药，对再摄取蛋白的亲和力可忽略不计，可能通过对多种受体（包括去甲肾上腺素（NE）α2和5-羟色胺（5-HT）2A/C受体）的拮抗剂活性间接增强单胺传递。历史上，米氮平也被认为是一种5-HT 2C拮抗剂，但最近的证据表明，米氮平是该受体亚型的反向激动剂。米氮平在几种啮齿动物药物滥用模型中减弱精神兴奋剂诱导的行为，并拮抗甲基苯丙胺诱导的大鼠生化和电生理改变，这表明混合作用的多巴胺能药物在成瘾药物治疗中具有很好的作用。临床前发现通过已发表的病例研究得到证实，这些病例研究记录了米氮平治疗在许多SUD中的成功结局。迄今为止，尚未进行评估米氮平在物质滥用药物治疗中的效用的大规模临床试验。然而，正如本文所述，积累的临床前和临床证据表明，米氮平或模仿其药理学特征的化合物可能有助于治疗成瘾。
Understanding substance use disorders (SUDs) and the problems associated with abstinence has grown in recent years. Nonetheless, highly efficacious treatment targeting relapse prevention has remained elusive, and there remains no FDA-approved pharmacotherapy for psychostimulant dependence. Preclinical and clinical investigations assessing the utility of classical antidepressants, which block monoamine reuptake, show mixed and often contradictory results. Mirtazapine (Remeron®) is a unique FDA-approved antidepressant, with negligible affinity for reuptake proteins, indirectly augments monoamine transmission presumably through antagonist activity at multiple receptors including the norepinephrine (NE)α2, and serotonin (5-HT)2A/C receptors. Historically, mirtazapine was also considered to be a 5-HT2C antagonist, but recent evidence indicates that mirtazapine is an inverse agonist at this receptor subtype. Suggesting a promising role for mixed-action serotonergic drugs for addiction pharmacotherapy, mirtazapine attenuates psychostimulant-induced behaviors in several rodent models of substance abuse, and antagonizes methamphetamine-induced biochemical and electrophysiological alterations in rats. Preclinical findings are confirmed through published case studies documenting successful outcomes with mirtazapine therapy across a number of SUDs. To date, a large scale clinical trial assessing the utility of mirtazapine in substance abuse pharmacotherapy has yet to be conducted. However, as reviewed here, accumulating preclinical and clinical evidence argues that mirtazapine, or compounds that emulate aspects of its pharmacological profile, may prove useful in helping treat addictions.
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影响因子：
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作者：
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通讯作者：
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作者：
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DOI：
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发表时间：
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DOI：
10.1523/jneurosci.5319-08.2009
发表时间：
2009-07-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Bickel WK;Pitcock JA;Yi R;Angtuaco EJ
通讯作者：
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