The selective 5-HT2C receptor agonist lorcaserin, in conjunction with lifestyle modification, was approved by the FDA in 2012 for weight management. It has been marketed in the US as Belviq® since 2013. This article provides a review of the preclinical and clinical pharmacology of lorcaserin, including its pharmacokinetic and safety profiles. Preclinical studies with lorcaserin initially focused on simple measures of food intake and body weight gain, but have now expanded to include studies on its effects on appetitive aspects of feeding behaviour and models of binge-eating. A significant number of studies have also shown that lorcaserin alters behaviours related to drug use and addiction, in rodents and non-human primates. Potential clinically-relevant effects of lorcaserin have also been reported in models of pain and seizure-like activity. Not surprisingly, the majority of clinical work with lorcaserin has focused on its effects on weight gain, and on physiological processes related to energy intake. However, results of clinical trials and experimental laboratory studies involving lorcaserin are now appearing which describe effects on a range of other behaviours and physiological functions. These include smoking cessation, cocaine self-administration, and behavioural and brain responses to food cues. All of this work suggests that lorcaserin may have therapeutic potential for a variety of disorders and conditions beyond obesity. Based on clinical experience, including the outcomes from several, large, well-powered clinical obesity trials at the approved 10mg BID dose both pre and post approval, a priori concerns about cardiac valvulopathy have largely been allayed. However, as with any recently approved first-in-class pharmacotherapy, there may be yet-unknown risks, as well as benefits, associated with use of lorcaserin. Nonetheless, the current safety profile and an expanding post approval safety data base should encourage further experimental laboratory-based and clinical trial-based research with lorcaserin in targeted populations to investigate its full therapeutic potential.

中文翻译：

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Lorcaserin：其临床前和临床药理学和治疗潜力的综述。

选择性5-HT2C受体激动剂lorcaserin结合生活方式的改变，于2012年被FDA批准用于体重管理。自2013年以来，它已在美国以Belviq®的形式销售。本文概述了氯卡色林的临床前和临床药理学，包括其药代动力学和安全性。lorcaserin的临床前研究最初侧重于食物摄入量和体重增加的简单测量，但现在已扩展到包括其对摄食行为和暴食模型的食欲影响的研究。大量研究还表明，氯卡色林可改变啮齿动物和非人类灵长类动物中与吸毒和成瘾有关的行为。在疼痛和癫痫样活动的模型中，氯卡色林的潜在临床相关作用也已有报道。毫不奇怪，氯卡色林的大多数临床工作都集中在其对体重增加的影响以及与能量摄入有关的生理过程上。但是，现在出现了涉及氯卡色林的临床试验和实验实验室研究的结果，这些结果描述了对一系列其他行为和生理功能的影响。这些措施包括戒烟，可卡因自我管理以及对食物线索的行为和大脑反应。所有这些工作表明，氯卡色林可能对肥胖以外的多种疾病和病症具有治疗潜力。基于临床经验，包括在批准前和批准后以批准的10mg BID剂量进行的几项大型，功能强大的临床肥胖症试验的结果，人们在很大程度上消除了对心脏瓣膜病的先前关注。然而，与最近批准的任何一流的药物疗法一样，使用氯卡色林可能会带来未知的风险和收益。尽管如此，当前的安全性概况和批准后的扩展安全性数据库应鼓励在目标人群中进一步使用氯卡色林进行基于实验的基于实验室和基于临床试验的研究，以研究其全部治疗潜力。