Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity.
Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity.
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DOI：
10.1002/prp2.84
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发表时间：
2015-02
影响因子：
2.6
通讯作者：
Dobson, Howard
中科院分区：
文献类型：
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作者：
Higgins, Guy A;Desnoyer, Jill;Van Niekerk, Annalise;Silenieks, Leo B;Lau, Winnie;Thevarkunnel, Sandy;Izhakova, Julia;DeLannoy, Ines Am;Fletcher, Paul J;DeLay, Josepha;Dobson, Howard
5-HT2C受体激动剂Lorcasein（Belviq®）是批准对物体的治疗的食品和药物施用g/kg sc B.I. D.与车辆处理的对照相比，体重的百分比显着降低（VER：10.6±0.4％； LOR 1：7.6±1.2％； LOR 2：5.4±0.6％，使用定量磁性（QMR）的量度均导致了量的变化。 Ardiography揭示了否瓣膜病的证据，即在7天的治疗期间确定目前的治疗方案的主动脉或二尖瓣反流总之，这些研究表明洛杉矶在DIO模型中的作用，即在主要终点测量％的背景下体重变化与临床上报道的相似（即3.0-5.2％vs. 3.2％）。目前的研究突出了肥胖模型（例如DIO）的翻译价值，并建议假设对非特异性药物效应（例如不适）（例如DIO）付出了合理的前瞻性转化，以帮助预测新化学物质的临床临床。
The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague–Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1–2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma Cmin and Cmax were in the range 13–160 ng/mL (1 mg/kg b.i.d.) and 34–264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0–5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity.