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首页> 外文学位 >Structural Determinants of Abuse-Related Neurochemical and Behavioral Effects of Para-Substituted Methcathinone Analogs in Rats.
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Structural Determinants of Abuse-Related Neurochemical and Behavioral Effects of Para-Substituted Methcathinone Analogs in Rats.

机译：滥用相关的神经化学和行为影响的结构决定因素的大鼠取代的美卡西酮类似物。

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摘要

Methcathinone (MCAT) is the beta-ketone analog of methamphetamine, and like its amphetamine analog, MCAT functions as a monoamine releaser that selectively promotes the release of dopamine (DA) and norepinephrine (NE) over serotonin (5-HT). MCAT produces amphetamine-like psychostimulant effects and is classified as a Schedule I drug of abuse by the United States Drug Enforcement Administration (DEA). Recently, synthetic MCAT analogs have emerged as designer drugs of abuse in Europe and the United States and have been marketed under deceptively benign names like "bath salts" in an attempt to evade legal restriction. These dangerous, recently emergent and novel drugs of abuse display varying selectivity to promote release of DA/NE vs. 5-HT, and selectivity for DA neurotransmission is believed to correlate with abuse liability. The goal of this dissertation was to conduct preclinical research to examine structural determinants of abuse-related behavioral and neurochemical effects produced by a series of synthetic MCAT analogs. Specifically, this project focused on one feature of the methcathinone scaffold: the para substituent of the benzene ring. A series of six novel MCAT analogs will be examined to evaluate how physicochemical parameters (steric, Es; electronic, sigma p; lipophilic, pip) of the para substituent influence in vitro monoamine transporter selectivity as well as in vivo neurochemical and behavioral effects. Results from this body of work implicate steric factors as being particularly important in determining a compound's abuse-related neurochemical and behavioral effects. Thus, these data not only offer an improved understanding of the mechanism of abuse-related drug effects produced by synthetic MCAT analogs, but also help in the generation of homology models of the human DA and 5-HT transporters (DAT and SERT, respectively).
机译：甲卡西酮（MCAT）是甲基苯丙胺的β-酮类似物，与其苯丙胺类似物一样，MCAT用作单胺释放剂，与5-羟色胺（5-HT）相比选择性促进多巴胺（DA）和去甲肾上腺素（NE）的释放。 MCAT会产生苯丙胺样的精神刺激药作用，并被美国药物管制局（DEA）列为附表I滥用药物。最近，在欧洲和美国，合成的MCAT类似物已成为设计滥用药物，并以“浴盐”之类的良性名称销售，以逃避法律限制。这些危险的，新近出现的新滥用药物显示出不同的选择性，以促进DA / NE与5-HT的释放，并且DA神经传递的选择性与滥用责任相关。本文的目的是进行临床前研究，以研究由一系列合成的MCAT类似物产生的与滥用相关的行为和神经化学作用的结构决定因素。具体而言，该项目着眼于甲基卡西酮骨架的一个特征：苯环的对位取代基。将检查一系列六个新颖的MCAT类似物，以评估对位取代基的物理化学参数（空间，Es，电子，sigma p，亲脂性，pip）如何影响体外单胺转运蛋白的选择性以及体内神经化学和行为的影响。该工作的结果表明空间因素对于确定化合物与滥用相关的神经化学和行为影响特别重要。因此，这些数据不仅提供了对合成MCAT类似物产生的滥用相关药物作用机理的更好理解，而且还有助于生成人DA和5-HT转运蛋白（分别为DAT和SERT）的同源性模型。 。

著录项

  • 作者

    Bonano, Julie S.;

  • 作者单位

    Virginia Commonwealth University.;

  • 授予单位 Virginia Commonwealth University.;
  • 学科 Pharmacology.;Behavioral psychology.;Neurosciences.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 143 p.
  • 总页数 143
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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