NEUROCHEMICAL ALTERATIONS BY DESIGNER DRUGS

对安非他明类设计药物的兴趣随着最近的 新闻界关注的焦点是3，4-亚甲二氧基甲基苯丙胺（MDMA;通常 称为“摇头丸”）。 虽然这组药物已经可以获得 很长一段时间以来，心理治疗师未经授权使用它的激增 越来越多的人为了享乐而使用它， 最近被缉毒局列入附表1管制。 在过去的15年里，我们一直在积极研究 大剂量的甲基苯丙胺对生物胺系统的毒性， 最近关于神经肽。 我们观察到， 生物合成酶的活性，生物胺的浓度， 它们的主要代谢物，以及这些代谢物的受体密度 在选定的大脑区域的神经递质;此外， 已观察到P物质和神经紧张素样免疫反应性。 由于MDMA在化学上与甲基苯丙胺相似，我们最近 研究了它对这些相同参数的影响;在初步研究中，我们 已经观察到脑色氨酸羟化酶活性的改变， 5-羟色胺的浓度，以及P-物质和 神经紧张素样免疫反应性类似于大 大量的甲基苯丙胺 我们现在建议彻底调查MDMA和其他药物的影响， 苯丙胺类特制药物[3，4-亚甲二氧基苯丙胺（MDA）， 2，5-二甲基-4-乙基安非他明（DOET）]对同一神经化学物质 这些参数会被甲基苯丙胺改变 我们是独一无二的 进行这些研究，因为在同一种动物中， 生物胺的生物合成、释放和代谢。 而且我们 最近获得了放射自显影技术， 受体的变化;此外，我们有抗血清，使我们能够测量 P物质和神经降压素浓度。 使用 在这些技术中，有可能获得对 作用，以及随后的机制，这些安非他明样 特制药物发挥作用。 不仅这些结果 研究对于了解 这些滥用药物的作用，但他们也可以提供宝贵的 关于多巴胺能， 脑的肾上腺素能和肽能系统。

Interest in amphetamine-like designer drugs has increased with the recent focus by the lay press on 3,4-methylenedioxymethamphetamine (MDMA; often referred to as "ecstasy"). Although this group of drugs has been available for a long time, the upsurge in its unauthorized use by psychotherapists and increasing use by the public for hedonistic purposes led to it being placed under Schedule 1 control recently by the Drug Enforcement Agency. Over the past 15 years, we have been actively investigating the effects of large toxicologic doses of methamphetamine on biogenic amine systems and more recently on neuropeptides. We have observed marked decreases in the activity of biosynthetic enzymes, concentrations of biogenic amines and their major metabolites, and in the density of receptors of these neurotransmitters in selected brain regions; moreover, alterations of substance P- and neurotensin-like immunoreactivity have been observed. Since MDMA is chemically similar to methamphetamine, we have recently studied its effects on these same parameters; in preliminary studies, we have observed alterations of brain tryptophan hydroxylase activity, concentration of 5-hydroxytryptamine, as well as in substance P- and neurotensin-like immunoreactivity similar to those observed after large doses of methamphetamine. We now propose to investigate thoroughly the effects of MDMA and other amphetamine-like designer drugs [3,4-methylenedioxyamphetamine (MDA), and 2,5-dimethyl-4-ethylamphetamine (DOET)] on the same neurochemical parameters, that are altered by methamphetamine. We are uniquely qualified to perform these studies since in the same animal we can measure biosynthesis, release and metabolism of biogenic amines. Moreover, we have recently acquired the autoradiographic techniques for measuring in situ receptor changes; furthermore, we have antisera which allow us to measure substance P and neurotensin concentrations by RIA analysis. With the use of these techniques, it is possible to gain significant insights into the effects, and subsequently the mechanism(s), by which these amphetamine-like designer drugs exert their effects. Not only will the results of these studies be important in understanding the effects and mechanism(s) of action of these abused drugs, but they could also provide valuable information on the interrelationships between the dopaminergic, serotonergic and peptidergic systems of the brain.