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匹莫范色林和氯卡色林可减轻雄性斯普拉格-道利大鼠的暴饮暴食症状。

Pimavanserin and Lorcaserin Attenuate Measures of Binge Eating in Male Sprague-Dawley Rats.

作者信息

Price Amanda E, Brehm Victoria D, Hommel Jonathan D, Anastasio Noelle C, Cunningham Kathryn A

机构信息

Center for Addiction Research, University of Texas Medical Branch, Galveston, TX, United States.

Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.

出版信息

Front Pharmacol. 2018 Dec 7;9:1424. doi: 10.3389/fphar.2018.01424. eCollection 2018.

Abstract

Binge eating disorder (BED) is characterized by dysregulated feeding and reward-related processes, and treatment is often challenged by limited therapeutic options. The serotonin (5-HT) 5-HT receptor (5-HTR) and 5-HTR are implicated in both feeding-related and reward-related behaviors and are thus poised to regulate BED-related behaviors. The purpose of this study was to assess the efficacy of the FDA-approved medications pimavanserin, a 5-HTR antagonist/inverse agonist, and lorcaserin, a 5-HTR agonist, in a rodent model of binge eating. The effects of pimavanserin (0.3-3.0 mg/kg), lorcaserin (0.25-1.0 mg/kg), and the lowest effective dose of pimavanserin (0.3 mg/kg) lorcaserin (1.0 mg/kg) were tested in a high-fat food (HFF) intermittent access binge eating model in adult male Sprague-Dawley rats ( = 64). We assessed three measures related to binge eating - binge episode occurrence, binge intake, and weight gain associated with HFF access. Pimavanserin decreased binge intake and weight gain associated with HFF access, but did not prevent binge episode occurrence. Lorcaserin decreased binge intake, but did not prevent binge episode occurrence or weight gain associated with HFF access. Combined pimavanserin lorcaserin prevented binge episode occurrence in addition to decreasing binge intake and weight gain associated with HFF access. These preclinical findings in male rats suggest that pimavanserin and lorcaserin may be effective in treating patients with BED. Our studies further indicate that administration of one or both drugs may be more effective in certain sub-populations of patients with BED because of the unique profile each treatment elicits. These data support future assessment in clinical populations with BED.

摘要

暴饮暴食症(BED)的特征是进食和奖励相关过程失调,治疗通常因治疗选择有限而面临挑战。血清素(5-HT)5-HT受体(5-HTR)和5-HTR与进食相关行为和奖励相关行为均有关联,因此有望调节与BED相关的行为。本研究的目的是评估美国食品药品监督管理局(FDA)批准的药物匹莫范色林(一种5-HTR拮抗剂/反向激动剂)和氯卡色林(一种5-HTR激动剂)在啮齿动物暴饮暴食模型中的疗效。在成年雄性斯普拉格-道利大鼠(n = 64)的高脂食物(HFF)间歇性获取暴饮暴食模型中,测试了匹莫范色林(0.3 - 3.0毫克/千克)、氯卡色林(0.25 - 1.0毫克/千克)以及匹莫范色林最低有效剂量(0.3毫克/千克)与氯卡色林(1.0毫克/千克)联合使用的效果。我们评估了与暴饮暴食相关的三项指标——暴饮暴食发作次数、暴饮暴食摄入量以及与获取HFF相关的体重增加。匹莫范色林减少了与获取HFF相关的暴饮暴食摄入量和体重增加,但并未阻止暴饮暴食发作。氯卡色林减少了暴饮暴食摄入量,但并未阻止暴饮暴食发作或与获取HFF相关的体重增加。匹莫范色林与氯卡色林联合使用除了减少与获取HFF相关的暴饮暴食摄入量和体重增加外,还阻止了暴饮暴食发作。雄性大鼠的这些临床前研究结果表明,匹莫范色林和氯卡色林可能对治疗BED患者有效。我们的研究进一步表明,由于每种治疗引发的独特特征,使用一种或两种药物对某些BED患者亚群可能更有效。这些数据支持未来在BED临床人群中进行评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0db/6293203/810a45d33936/fphar-09-01424-g001.jpg

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