Chemistry and Pharmacology of Newly Emerging Psychoactive Plants

描述（由申请人提供）：近年来，新的精神活性植物及其活性次级代谢产物已经出现在街道上。一个例子是强烈的致幻薄荷鼠尾草（Salvia divinorum）及其活性代谢物鼠尾草素A。这种不受联邦和大多数州法律管制的新型致幻剂的使用正在全国和全球范围内蔓延。这些植物很容易在许多互联网网站上获得，在不久的将来很有可能成为街头毒品。尽管它们容易获得，但这些物质的化学和药理学在很大程度上是未知的。在大多数情况下，这些植物的活性成分和它们与中枢神经系统相互作用的机制都还没有确定。这个项目的目的是研究具有致幻或镇静作用的鲜为人知的新兴精神活性植物的化学和药理学。在这个项目中，我们选择了15种化学和药理学知之甚少的强效致幻/镇静植物。我们建议根据查佩尔山的北卡罗来纳州大学的NIMH精神活性药物筛选计划，对这些植物的CNS受体电池进行生物学评价，并分离出负责致幻和其他精神作用的活性次级代谢产物。从长远来看，本项目中发现和开发的CNS受体新配体将有助于更好地了解中枢神经系统功能及其疾病。为实现这些目标，将努力实现以下具体目标：1.从植物园、私人收藏品或商业经纪人处收购选定的植物物种。2.选择性提取生物材料。3.提取物对CNS神经递质受体亲和力的生物学评价。4.活性次级代谢产物的生物测定引导的分级分离。5.代谢产物的结构解析及其在特定受体系统中的生物学再评价。6.铅化合物的化学转化。该项目产生的数据将成为进一步研究的基础，并为寻求更广泛的资金提供初步结果。随着街头新出现的致幻剂越来越多，人们，特别是青少年的健康问题变得非常重要。对于许多使用的致幻植物，我们不知道它们在中枢神经系统中的作用机制，它们成为滥用成瘾药物的潜力，它们对人体重要器官和系统的毒性或其他副作用。我们的新出现的精神活性植物的化学和药理学项目将解决这些问题，并为这一领域的进一步研究提供信息。

DESCRIPTION (provided by applicant): In recent years new psychoactive plants and their active secondary metabolites have been emerging on the streets. An example is the strong hallucinogenic mint Salvia divinorum and its active metabolite salvinorin A. This use of new hallucinogens unregulated by Federal and most State laws is spreading across the country and globally. The plants are easily obtained on numerous internet sites and have a high potential of becoming street drugs in the near future. Despite their ready availability the chemistry and pharmacology of these substances are largely unknown. In most cases neither the active constituents of these plants nor the mechanism of their interaction with the central nervous system have been determined. The purpose of this project is study the chemistry and pharmacology of lesser known emerging psychoactive plants with purported hallucinogenic or sedative activity. For this project we have selected 15 potent hallucinogenic/sedative plant species with little known chemistry and pharmacology. We propose to biologically evaluate these plants against the battery of CNS receptors under NIMH Psychoactive Drug Screening Program at the University of North Carolina at Chapel Hill and isolate the active secondary metabolites responsible for hallucinogenic and other psychotropic effects. In the long-term new ligands to CNS-receptors discovered and developed in this project will contribute to better knowledge of the central nervous system functions and its disorders. To achieve these goals, the following specific aims will be pursued: 1. Acquisition of selected plant species from botanical gardens, private collections or commercial brokers. 2. Selective extraction of biological material. 3. Biological evaluation of extracts for affinity to CNS neurotransmitters receptors. 4. Bioassay-guided fractionation and isolation of active secondary metabolites. 5. Structure elucidation of isolated metabolites and their biological re-evaluation in the specific receptor systems. 6. Chemical transformations of lead compounds. The data generated by this project will form a basis for further research and provide preliminary results for seeking more extensive funding. PUBLIC HEALTH RELEVANCE With the growing number of newly emerging hallucinogens on the streets, the concern of the health of people, especially youth, becomes a very important issue. For many hallucinogenic plants used we do not know their mechanism of action in central nervous system, their potential to become addictive drugs of abuse, their toxicity to vital organs and systems of human body or other side effects. Our project on the chemistry and pharmacology of newly emerging psychoactive plants will address these issues and provide information to further research in this area.