P 3: PSYCHOACTIVITY OF CANNABINOIDS & INTERACT W/ DELTA-9-TETRAHYDROCANNABINOL

P 3：大麻素的心理活性

基本信息

批准号：
7610759
负责人：
SAMIR A ROSS
金额：
$ 20.09万
依托单位：
UNIVERSITY OF MISSISSIPPI
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2008-06-30
项目状态：
已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Twenty four compounds have been isolated from Cannabis extracts using a combination of different chromatographic techniques, including vaccum liquid chromatography, open column chromatography, and HPLC (normal and reversed phase). The structures of the isolated compounds were established by UV, IR, GC-MS, HR-ESI-MS, 1D and 2D- NMR experiments. Nine out of the 24 identified compounds were isolated for the first time from Cannabis. These nine compounds include four hydroxylated cannabinoids, epoxycannabigerolic acid, three tetrahydrocannabinoic acid esters, and one THC aldehyde. The remaining 14 compounds are known and include 11 cannabinoids: dehydrocannabifuran, cannabicitran, cannabicyclol, cannabicyclolic acid, cannabigerol, cannabigerolic acid, cannabinol, cannabinolic acid, THC acid A, THC, and cannabiripsol; 3 non-cannabinoid phenolics: cannabispiran I, cannabispiranol, and canniflavin B; and one sterol: beta-sitosterol. All of the isolated compounds were subjected to CB1 receptor affinity assays (primary screen). Only four compounds showed highly significant inhibition in the assays, highly comparable with that of THC, and one showed moderate inhibition. The five active compounds are hydroxylated cannabinoids and four of them are new natural products. The IC50s of the active compounds are 589 nM, 624 nM, 73 nM, 1256 nM and 6408 nM. These compounds were subjected to GTP¿S assays in order to determine if they are agonists or antagonists.

该副本是使用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这是调查员的机构。使用不同色谱技术的组合，包括液相色谱，开放柱色谱和HPLC（正常和反向相），从大麻提取物中分离出了二十四种化合物。分离化合物的结构是由UV，IR，GC-MS，HR-ESI-MS，1D和2D-NMR实验建立的。在这24个确定的化合物中，有9种是从大麻中分离出来的。这些九种化合物包括四种羟基化大麻素，环化汉库抗酸，三个四氢大麻素酸酯和1个THC醛。其余的14种化合物是已知的，包括11种大麻素：脱氢大麻素，大麻，大麻酸，大麻酸，大麻酸，大麻抗酸，大麻抗酸，大麻抗酸，大麻醇，大麻醇，大麻酸，THC酸A，THC，THC，THC和Cannabiripsol；非大麻素酚类：大麻I，大麻甲醇和罐头B；和一个固醇：β-塞托醇。所有分离的化合物均接受CB1受体亲和力测定（主要筛选）。只有四种化合物在测定中表现出高度显着的抑制作用，与THC的抑制作用高度可比，另一种显示出中度抑制作用。这五种活性化合物是羟化大麻素，其中四种是新的天然产品。活性化合物的IC50为589 nm，624 nm，73 nm，1256 nm和6408 nm。这些化合物受到GTP的测定，以确定它们是激动剂还是拮抗剂。