Dissecting the Abuse Liability of Synthetic Cathinone Stimulants

剖析合成卡西酮兴奋剂的滥用责任

• 批准号: 9161060
• 负责人: TOBIN J DICKERSON
• 金额: $ 43.31万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9161060
• 关键词: Affect; Americas; Amphetamines; Bathing; Brain; Carbon; Characteristics; Cocaine; Dependence; Drug Addiction; Environment; Exhibits; Geographic state; Goals; Health; Human; Intake; Intravenous; Investigation; Legal; Marketing; Medical emergency; Methamphetamine; Modeling; Parents; Personal Satisfaction; Pharmaceutical Preparations; Population; Property; Psychological reinforcement; Psychotropic Drugs; Rattus; Reinforcement Schedule; Reporting; Risk; Rodent; Rodent Model; Salts; Schedule; Self Administration; Siblings; Speed; Structure; Tail; Testing; United States; Work; addiction; cathinone; college; design; drug efficacy; drug modification; ecstasy; in vivo; lipophilicity; meetings; monomethylpropion; neurochemistry; psychostimulant; reinforcer; symposium

The use of synthetic psychoactive cathinone drugs (“bathsalts”) continues to expand worldwide and in the United States of America despite legal control efforts internationally, at the US federal level, within multiple US states and even the local US jurisdictions. The established stimulants such as cocaine and methamphetamine are highly addictive, can be acutely lethal and can result in long- term brain alterations with many implications for health and well-being. Recent studies show that 3,4- methylenedioxypyrovalerone (MDPV) is a highly potent and efficacious reinforcer, predicting abuse liability equal to or greater than that of cocaine and methamphetamine. Compounds such as Mephedrone and Methylone produce subjective properties that are similar to 3,4- methylenedioxymethamphetamine (MDMA) but have exhibit much greater propensity for compulsive use in human report and rodent self-administration studies. This project responds to the goals of PAR-14-106 Synthetic Psychoactive Drugs and Strategic Approaches to Counteract Their Deleterious Effects by determining structural determinants of the addiction liability of synthetic cathinones. Tremendous diversity of cathinone structure exists in the recreational market, driven in part by legal control of earlier-appearing drugs. This reality demands approaches which can both advance understanding of the actions of currently popular drugs and generate better predictions regarding which design motifs may convey increased abuse liability in emerging compounds. To that end, studies under Aim I and Aim II will elucidate the contributions of the 3,4-methylenedioxy and 4- methyl aromatic ring substitutions, respectively, to the reinforcement potency and efficacy of cathinones. One distinct feature of MDPV is an extended carbon chain which confers enhanced lipophilicity. The goal of Aim III is to determine if stimulant drug efficacy in intravenous self- administration is affected by lipophilicity, which affects speed of brain entry. In total, these proposed studies on the reinforcing effects of various synthetic cathinones will advance our understanding of the health risks associated with designer stimulant drugs.

使用合成精神活性凯瑟诺酮药物（“浴）”的使用继续扩展到全球范围内 在美国，尽管国际法律控制努力，美国联邦 级别，在美国多个州，甚至是当地的美国司法管辖区。建立的兴奋剂这样 由于可卡因和甲基苯丙胺具有高度添加剂，因此可能是敏锐的致命，可能会导致长期 术语变化对健康和福祉有许多影响。最近的研究表明，3,4-- 甲基二邻甲甲基甲酮（MDPV）是一种高潜力和有效的增强剂，可预测滥用 责任等于或大于可卡因和甲基苯丙胺的责任。诸如 甲酮和甲基酮产生的主观特性，类似于3,4-- 甲基二甲基甲基苯丙胺（MDMA），但暴露了更大的强迫性倾向 在人类报告和啮齿动物自我管理研究中使用。该项目回应了 PAR-14-106合成精神活性药物和战略方法来抵消其有害的 通过确定结构决定者的成瘾责任的效果。 在娱乐市场中存在巨大的凯瑟酮结构的多样性，部分由合法驱动 控制较早的药物。这种现实需要既可以进步的方法 了解当前受欢迎的药物的行动，并就有关 哪种设计图案可能会传达出新的化合物中滥用责任的增加。为此， AIM I和AIM II下的研究将阐明3,4-甲基二氧和4--的贡献 甲基芳香环取代，分别对增强效力和效率 chater。 MDPV的一个独特特征是扩展的碳链，它承认增强 亲脂性。 AIM III的目标是确定静脉自我自我的刺激性药物效率是否存在 给药受亲脂性的影响，这会影响大脑进入速度。总共提出了这些 关于各种合成阴茎的增强作用的研究将提高我们对 与设计师兴奋剂有关的健康风险。