B CARBOLINE HALLUCINOGENS

β-卡洛林致幻剂仍然是经典的最后一类 未经系统研究的致幻剂 全面的态度。这些被称为幻想的特工- 增强剂，正受到媒体越来越多的关注。由于 它们的合成相对容易，而且因为人们对 致幻剂，β-卡洛林致幻剂可能证明 是这个国家未来滥用的毒品，或者可能成为 新设计药物的开发。人们对他们的情况知之甚少 结构-活性关系(SAR)，基本上什么都不知道 关于他们的行动机制。β-卡洛林致幻剂， 因为它们具有吲哚乙基胺核，所以被归类为 经典迷幻剂(即迷幻剂家族的成员 吲哚乙基胺LSD和苯烷胺1-(2，5-二甲氧基-4- 甲苯基)-2-氨基丙烷或DOM属于)。因为重大进展 近年来在了解香港特别行政区和 经典致幻剂的作用机制，它可能是额外的或 将这一信息应用于β-卡洛林致幻剂，如果确实如此， 他们可以被证明是同一个迷幻剂家族的成员。 初步数据表明，一些β-碳氢化合物的行为确实类似于 传统的致幻剂，而其他数据表明，差异可能 是存在的。也就是说，仅有的几个SAR结果是不一致的 已知的其他经典致幻剂；然而，有两种 β-卡洛林致幻剂的例子(即骆驼蓬碱和6- 甲氧基哈马兰)，与(+)LSD一样，产生类似于 由DOM制作。这项研究的总体目标是系统地 检测β-卡洛林致幻剂并鉴定其SAR和 确定它们是否通过与其他古典音乐相同的机制起作用 迷幻剂或通过独特的作用机制。从这个意义上说，毒品 以大鼠为对象的歧视研究和放射性配基结合 为了确定受体的亲和力，将进行。具体来说，测试 将进行刺激泛化和刺激对抗 被训练成从车辆中辨别骆驼石的动物，以便 确定刺激作用机制，测试刺激泛化 将用经过训练的动物来区分DOM或 从车辆中提取骆驼蓬碱以确定刺激效果的相似性，以及 将进行放射性配基结合研究，并尝试关联 具有刺激效力，以查看关系是否像与其他人一样存在 经典的迷幻剂。检验特定假设所需的化合物 都计划用来合成。药理学和SAR的比较将是 由其他经典迷幻剂和非致幻剂制成- 卡波林。因为初步数据显示其中某些毒剂 结合5-羟色胺和色胺受体，该项目最初将 关注这两种神经递质机制。

The beta-carboline hallucinogens remain as the last category of classical hallucinogenic agents that has not been studied in a systematic and comprehensive manner. These agents, which have been termed fantasy- enhancing agents, are receiving increased attention in the media. Due to their relative ease of synthesis, and because of a resurgent interest in hallucinogenic agents, the beta-carboline hallucinogens may either prove to be future drugs of abuse in this country or may serve as templates for the development of new designer drugs. Little is known about their structure-activity relationships (SAR) and essentially nothing is known regarding their mechanism of action. The beta-carboline hallucinogens, because they possess an indolealkylamine nucleus, have been categorized as classical hallucinogens (i.e. members of a hallucinogen family to which the indolealkylamine LSD, and the phenalkylamine 1-(2,5-dimethoxy-4- methylphenyl)-2-aminopropane or DOM, belong). Because significant progress has been made in recent years with respect to understanding the SAR and mechanism of action of classical hallucinogens, it may be extra olate or apply this information to the beta-carboline hallucinogens if, indeed, they can be demonstrated to be members of the same hallucinogen family. Preliminary data suggest that some beta-carbolines do behave like classical hallucinogens whereas other data indicate that differences may exist. That is, what little SAR results are available are inconsistent with what is known about other classical hallucinogens; and yet, two examples of beta-carboline hallucinogens (i.e. harmaline and 6- methoxyharmalan), like (+ )LSD, produce stimulus effects similar to those produced by DOM. The overall goals of this study are to systematically examine beta-carboline hallucinogens and to identify their SAR and to determine if they act via a mechanism common to other classical hallucinogens or via a unique mechanism of action. To this extent, drug discrimination studies employing rats as subjects, and radioligand binding to determine receptor affinity, will be undertaken. Specifically, tests of stimulus generalization and stimulus antagonism will be conducted with animals trained to discriminate harmaline from vehicle in order to identify stimulus mechanisms of action, tests of stimulus generalization will be conducted with animals trained to discriminate either DOM or harmaline from vehicle to determine similarity of stimulus effects, and radioligand binding studies will be performed, and correlations attempted with stimulus potency, to see if relationships exist as they do with other classical hallucinogens. Compounds required to test specific hypotheses are planned for synthesis. Pharmacological and SAR comparisons will be made with other classical hallucinogens and with non-hallucinogenic beta- carbolines. Because preliminary data suggest that certain of these agents bind at serotonin and tryptamine receptors, the project will initially focus on these two neurotransmitter mechanisms.