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: 9932085
• 负责人: MICHAEL A. TAFFE
• 金额: $ 35.44万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-18 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9932085
• 关键词: Acute; Affect; Americas; Amphetamines; Bathing; Brain; Carbon; Characteristics; Cocaine; Dependence; Drug Addiction; Environment; Exhibits; Geographic state; Goals; Health; Human; Intake; International; Intravenous; Investigation; Legal; Medical emergency; Methamphetamine; Modeling; Parents; Personal Satisfaction; Pharmaceutical Preparations; Pharmacology; 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.

合成精神活性卡西酮药物（“浴盐”）的使用继续在全球范围内扩大 尽管国际上采取了法律控制措施，但在美利坚合众国，美国联邦 级别，在美国多个州甚至美国当地管辖范围内。 因为可卡因和甲基苯丙胺具有高度成瘾性，可能致命，并可能导致长期 术语“大脑改变”对健康和福祉具有多种影响。最近的研究表明，3,4-。 亚甲二氧基吡咯戊酮 (MDPV) 是一种高效且有效的强化剂，可预测滥用 责任等于或大于可卡因和甲基苯丙胺等化合物。 甲麻黄酮和甲酮产生类似于 3,4- 的主观特性 亚甲二氧基甲基苯丙胺 (MDMA)，但表现出更大的强迫倾向 在人类报告和啮齿动物自我管理研究中的使用该项目响应了以下目标。 PAR-14-106 合成精神活性药物及其有害的战略方法 通过确定合成卡西酮成瘾倾向的结构决定因素的影响。 娱乐市场中卡西酮结构存在巨大多样性，部分原因是法律规定 这一现实需要能够同时推进的方法。 了解当前流行药物的作用并产生更好的预测 其设计主题可能会增加新兴化合物的滥用可能性。 Aim I 和 Aim II 下的研究将阐明 3,4-亚甲二氧基和 4- 甲基芳环取代分别对增强效力和功效 MDPV 的一个显着特征是碳链延长，从而增强了卡西酮的性能。 目标 III 的目标是确定兴奋剂药物在静脉自体注射中的功效。 给药受到亲脂性的影响，亲脂性会影响大脑进入的速度。 对各种合成卡西酮的增强作用的研究将增进我们对 与设计兴奋剂药物相关的健康风险。