Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Am J Health Syst Pharm. 2011 Nov 1;68(21):2029-37. doi: 10.2146/ajhp100638.
The pharmacology, pharmacokinetics, and adverse effects of the selective serotonin (5-HT) agonist lorcaserin are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials.
Lorcaserin is highly selective for a subtype of 5-HT receptors important in appetite regulation, with low affinity for other 5-HT-receptor subtypes whose activation is thought to underlie serious cardiovascular adverse effects; such effects have been seen with nonselective serotonergic agents for weight loss (e.g., fenfluramine). In two Phase III trials of lorcaserin, the cumulative proportion of patients who achieved weight loss of ≥5% over 12 months was about 47% with lorcaserin use versus 20-25% among placebo users (p < 0.0001 for both trials). Lorcaserin was generally well tolerated in the clinical trials to date; nausea and vomiting, headache, and dizziness were the most commonly reported adverse effects. In two of the three Phase III trials to date, lorcaserin use was not found to increase the risk of cardiac valvulopathy; however, in the other Phase III trial, which focused on patients with diabetes, lorcaserin use was associated with an increased rate of new valvulopathy. In a carcinogenicity evaluation involving laboratory rats, lorcaserin was linked to the development of various malignancies, a finding with uncertain implications for its potential future use in humans.
Lorcaserin, a 5-HT(2C) agonist, has demonstrated efficacy in patients who are obese or are overweight with associated comorbidities. Phase III trials have found that more than 35% of patients lost greater than 5% of their baseline weight. The maker of lorcaserin has indicated it will continue to seek U.S. marketing approval of the drug for the indications of long-term weight loss and weight-loss maintenance in specific patient populations.
本文回顾了选择性 5-羟色胺（5-HT）激动剂洛卡塞林的药理学、药代动力学和不良反应，重点介绍了 III 期临床试验的疗效和安全性数据。
洛卡塞林对 5-HT 受体的一种亚型具有高度选择性，这种亚型在食欲调节中起重要作用，对其他 5-HT 受体亚型的亲和力较低，而这些受体亚型的激活被认为是导致严重心血管不良反应的原因；非选择性 5-羟色胺能减肥药（如芬氟拉明）就出现过这种不良反应。在洛卡塞林的两项 III 期临床试验中，使用洛卡塞林治疗 12 个月后体重减轻≥5%的患者累计比例约为 47%，而安慰剂组为 20-25%（两项试验均<0.0001）。迄今为止，洛卡塞林在临床试验中总体耐受性良好；最常见的不良反应是恶心、呕吐、头痛和头晕。迄今为止的三项 III 期试验中的两项未发现洛卡塞林增加心脏瓣膜病的风险；然而，在另一项专注于糖尿病患者的 III 期试验中，洛卡塞林的使用与新瓣膜病的发生率增加有关。在一项涉及实验室大鼠的致癌性评估中，洛卡塞林与各种恶性肿瘤的发展有关，这一发现对其未来在人类中的潜在应用具有不确定的影响。
洛卡塞林是一种 5-HT（2C）激动剂，已在肥胖或超重合并有合并症的患者中显示出疗效。III 期试验发现，超过 35%的患者体重减轻超过基线体重的 5%。洛卡塞林的制造商表示，将继续寻求美国批准该药物用于特定患者人群的长期减肥和减肥维持。
