Lorcaserin, a selective serotonin 2C (5-HT_2C) receptor agonist, was approved for treating obesity and has been investigated for treating substance use disorders including those involving opioids. Although lorcaserin was withdrawn from the market, interest in the therapeutic potential of drugs acting at 5-HT_2C receptors continues, supporting the need to further characterize potential adverse effects especially when combined with drugs of abuse. This study examined acute effects of lorcaserin on opioid-induced ventilatory depression, which is the primary cause of overdose, and opioid self-administration, which models factors contributing to opioid abuse, in male and female rhesus monkeys. In one group (n = 4), effects of morphine (0.178 to 5.6 mg/kg, s.c.), fentanyl (0.0032 to 0.1 mg/kg, s.c.), and lorcaserin (0.1 to 1.78 mg/kg, s.c.) alone as well as effects of lorcaserin with each opioid on ventilation were determined using head plethysmography. Another group (n = 5) responded under a food versus fentanyl (0.1 to 3.2 μg/kg/infusion, i.v.) choice procedure, and lorcaserin (0.32 to 1.78 mg/kg, i.v.) was given as a pretreatment. Lorcaserin dose-dependently decreased minute volume to below 70 % of baseline when administered alone and increased the potency of morphine and fentanyl. Consistent with previous studies, lorcaserin failed to alter choice of fentanyl over food. This study demonstrates the novel finding that lorcaserin alone decreases ventilation and enhances the ventilatory-depressant effects of opioids. Taken together with previous studies, these results suggest that combining a 5-HT_2C receptor agonist such as lorcaserin with an opioid could increase the risk of ventilatory depression without the benefit of decreasing abuse.

氯卡色林是一种选择性血清素 2C (5-HT _2C ) 受体激动剂，已被批准用于治疗肥胖症，并已被研究用于治疗药物滥用障碍，包括涉及阿片类药物的药物滥用障碍。_{尽管氯卡色林已从市场上撤回，但人们对作用于 5-HT 2C受体}的药物的治疗潜力的兴趣仍在继续，这支持需要进一步表征潜在的不良反应，特别是与滥用药物合用时。这项研究在雄性和雌性恒河猴中研究了氯卡色林对阿片类药物引起的通气抑制（这是药物过量的主要原因）和阿片类药物自我给药（模拟导致阿片类药物滥用的因素）的急性影响。在一组（ n  = 4）中，还单独使用吗啡（0.178 至 5.6 毫克/公斤，皮下注射）、芬太尼（0.0032 至 0.1 毫克/公斤，皮下注射）和氯卡色林（0.1 至 1.78 毫克/公斤，皮下注射）使用头部体积描记法确定氯卡色林与每种阿片类药物对通气的影响。另一组（n  = 5）在食物与芬太尼（0.1至3.2微克/千克/输注，静脉注射）选择程序下做出反应，并给予氯卡色林（0.32至1.78毫克/千克，静脉注射）作为预处理。当单独给药时，氯卡色林剂量依赖性地将每分钟通气量降低至基线的 70% 以下，并增加吗啡和芬太尼的效力。与之前的研究一致，氯卡色林未能改变芬太尼对食物的选择。这项研究证明了新发现，即单独使用氯卡色林会降低通气量并增强阿片类药物的通气抑制作用。与之前的研究相结合，这些结果表明，将 5-HT _2C受体激动剂（例如氯卡色林）与阿片类药物联合使用可能会增加通气抑制的风险，而不会减少滥用。