Evaluation of the 5-HT2C agonist lorcaserin as potential treatment for cocaine ab

5-HT2C 激动剂氯卡色林作为可卡因抗体潜在治疗方法的评估

• 批准号: 9008117
• 负责人: CHARLES P FRANCE
• 金额: $ 14.75万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9008117
• 关键词: Agonist; Attenuated; Behavior; Clinical; Cocaine; Cocaine Abuse; Data; Dependence; Development; Dopamine; Dose; Drug abuse; Evaluation; Health; Human; Hyperactive behavior; Macaca mulatta; Pharmaceutical Preparations; Procedures; Property; Recovery; Relapse; Research; Rodent; Self Administration; Serotonin; Serotonin Receptor 5-HT2C; Stimulus; attenuation; atypical antipsychotic; clinical effect; cost; dopamine system; drug addict; drug craving; drug discrimination; drug of abuse; effective therapy; human data; nonhuman primate; public health relevance; research clinical testing; research study; transmission process

DESCRIPTION (provided by applicant): The positive reinforcing properties of drugs of abuse are thought to result from enhanced activity in meso-limbic dopamine (DA) systems. In addition to direct blockade of DA transmission by classical and atypical antipsychotics, an alternative approach to diminishing central DA activity is via stimulation of serotonin 5-HT2C receptors. The research described in the present proposal will evaluate one such 5-HT2C agonist lorcaserin, already well advanced in clinical development in other indications, for its attenuation of cocaine abuse-related behavior in the rhesus monkey. Data obtained in this non-human primate (NHP) should better predict clinical effects in humans than data from rodents. The aim is to determine whether the NHP data would provide encouragement, or not, for the clinical testing of lorcaserin for treating cocaine abuse in humans. The experiments will evaluate lorcaserin for attenuation of cocaine-induced hyperactivity; cocaine maintained self-administration behavior and the internal stimulus properties of cocaine in a drug discrimination procedure. To demonstrate that lorcaserin could be useful for treating cocaine abuse in humans, these experiments should show that lorcaserin is effective in attenuating cocaine abuse- related behavior in NHP at doses without intrinsic effects on behavior.

描述（由申请人提供）：认为滥用药物的积极加强特性被认为是由中膜多巴胺（DA）系统的活动增强而导致的。除了经典和非典型抗精神病药对DA传播的直接阻断外，减少中央DA活性的另一种方法是通过刺激5-羟色胺5-HT2C受体。本提案中描述的研究将评估一种这样的5-HT2C激动剂Lorcaserin，在其他适应症的临床发育方面已经很好地提高了其对可卡因虐待相关的行为的衰减。在这种非人类灵长类动物（NHP）中获得的数据应比啮齿动物的数据更好地预测人类的临床影响。目的是确定NHP数据是否会鼓励Lorcaserin的临床测试，以治疗人类可卡因滥用。该实验将评估劳卡森因可卡因诱导的多动症的衰减。可卡因在药物歧视程序中保持自我给药行为和可卡因的内部刺激特性。为了证明Lorcaserin对于治疗人类的可卡因滥用可能是有用的，这些实验应表明劳卡森蛋白有效地以剂量减弱与行为内在影响的剂量的NHP相关行为。