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: 8714994
• 负责人: CHARLES P FRANCE
• 金额: $ 40.56万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714994
• 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）：滥用药物的正强化特性被认为是由于中脑边缘多巴胺（DA）系统的活性增强。除了通过经典和非典型抗精神病药直接阻断DA传递外，减少中枢DA活性的另一种方法是通过刺激5-羟色胺5-HT 2C受体。本提案中描述的研究将评估一种这样的5-HT 2C激动剂氯卡色林，其在其他适应症的临床开发中已经很先进，用于减轻恒河猴中可卡因滥用相关行为。在这种非人灵长类动物（NHP）中获得的数据应该比啮齿类动物的数据更好地预测人类的临床效果。其目的是确定NHP数据是否会为氯卡色林治疗人类可卡因滥用的临床试验提供鼓励。该实验将评价氯卡色林对可卡因诱导的多动症的减弱作用;可卡因在药物辨别程序中维持自我给药行为和可卡因的内部刺激特性。为了证明氯卡色林可用于治疗人类的可卡因滥用，这些实验应显示氯卡色林在对行为没有内在影响的剂量下有效减弱NHP中的可卡因滥用相关行为。