The use of serotonergic drugs to treat obesity--is there any hope?
The use of serotonergic drugs to treat obesity--is there any hope?
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DOI：
10.2147/dddt.s11859
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发表时间：
2011-02-10
期刊：
影响因子：
--
通讯作者：
Liang NC
中科院分区：
文献类型：
--
作者：
Bello NT;Liang NC
手术介入治疗肥胖的策略正在越来越多地实施。对于大多数超重或肥胖的人来说，这些手术的安全性和可行性值得怀疑。另一方面，长期药物治疗方案的使用可以针对更大比例的肥胖人群，并提供早期干预，帮助个人保持健康的生活方式，以促进体重减轻。在过去的35年里，作用于血清素中枢通路的药物一直是治疗肥胖的主要方法。然而，这些药物的临床疗效一直受到药物相关并发症的潜在影响。西布曲明和氯卡色林这两种药物通过不同的机制作用于中枢血清素能系统，以减少食物摄入和减轻体重。西布曲明是一种5 -羟色胺和去甲肾上腺素再摄取抑制剂，而氯卡色林是一种选择性5HT2C受体激动剂。最近全球范围内西布曲明的停药和FDA对氯卡色林的拒绝不仅改变了以血清素为基础的治疗方法的前景，而且改变了肥胖药物治疗的总体前景。本综述的目的是关注血清素能系统在喂养控制中的重要性及其作为肥胖药物治疗靶点的潜力。为了产生有益的药物治疗，需要在精炼和筛选更多选择性受体激动剂方面取得进展，并更好地了解血清素能药物的潜在脱靶效应。
Surgical interventional strategies for the treatment of obesity are being implemented at an increasing rate. The safety and feasibility of these procedures are questionable for most overweight or obese individuals. The use of long-term pharmacotherapy options, on the other hand, can target a greater portion of the obese population and provide early intervention to help individuals maintain a healthy lifestyle to promote weight loss. Medications that act on the central serotonergic pathways have been a relative mainstay for the treatment of obesity for the last 35 years. The clinical efficacy of these drugs, however, has been encumbered by the potential for drug-associated complications. Two drugs that act, albeit by different mechanisms, on the central serotonergic system to reduce food intake and decrease body weight are sibutramine and lorcaserin. Sibutramine is a serotonin and norepinephrine reuptake inhibitor, whereas lorcaserin is a selective 5HT2C receptor agonist. The recent worldwide withdrawal of sibutramine and FDA rejection of lorcaserin has changed the landscape not only for serotonin-based therapeutics specifically, but for obesity pharmacotherapy in general. The purpose of this review is to focus on the importance of the serotonergic system in the control of feeding and its potential as a target for obesity pharmacotherapy. Advances in refining and screening more selective receptor agonists and a better understanding of the potential off-target effects of serotonergic drugs are needed to produce beneficial pharmacotherapy.