CANNABINOID INVESTIGATIONS

大麻素调查

• 批准号: 3213092
• 负责人: RAPHAEL MECHOULAM
• 金额: $ 9.04万
• 依托单位: HEBREW UNIVERSITY OF JERUSALEM
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3213092
• 关键词: analgesics; antiemetics; antiinflammatory agents; behavior test; cannabinoids; chemical structure function; drug design /synthesis /production; drug metabolism; drug receptors; inhibitor /antagonist; laboratory mouse; laboratory rat; opiate alkaloid; pigeons; psychotropic drugs; radiotracer; stereoisomer; tritium

I. It is generally considered that the natural (3R,4R) Delta1- tetrahydrocannabinol (Delta1-THC) is only about 13-20 times more active than the synthetic (3S,4S) enantiomer. On the basis of preliminary work we consider that the stereospecificity of THC activity is, in actuality, absolute. We plan to prepare stereochemically pure enantiomers and test them in the mouse ring test and by drug discrimination techniques. II. We plan to prepare two new types of cannabinoid probes (labelled with tritium on the methyl group of cyclohexene ring and on one of the methyl groups of the pyran ring). We shall use these probes for the identification of possible new subgroups of the cannabinoid receptor. III. Little is known on the antiemetic SAR of cannabinoids. We plan to test for antiemetic activity in pigeons various natural and synthetic cannabinoids in order to establish SAR rules. On the basis of preliminary work we expect to be able to show that separation can be achieved between cannabimimetic and antiemetic activity. IV. Work by our group and that of S. Burstein has shown that separation between cannabimimetic and analgetic activity is possible. We plan to prepare compounds, mainly of two types (cannabinoid- 7-oic acids and monoalkyl ethers of cannabidiol type of compounds) for which preliminary indications exists for separation of activity. V. We have shown that (+)-7-OH-Delta6-THC dimethylhepty homolog (HU-211) blocks respiratory depression by morphine. We plan to expand our research in this area and to look for similar blocking of opiate activity in analgesia and gastrointestinal activity.

I.通常认为自然（3R，4R）delta1- 四氢大麻酚（Delta1-THC）的活性仅大约13-20倍 比合成（3s，4s）对映异构体。 在初步工作的基础上我们 考虑到THC活动的立体特异性实际上是 绝对。 我们计划准备立体化学上的纯对映异构体并进行测试 它们在小鼠环测试和通过药物歧视技术中进行。 ii。 我们 计划准备两种新型的大麻素探针（用Tritium标记 在环己烯环的甲基和一组甲基上 Pyran戒指）。 我们将使用这些探测器来识别 大麻素受体可能的新亚组。 iii。 鲜为人知 在大麻素的抗疫苗SAR上。 我们打算测试抗过敏性 鸽子的活性各种天然和合成大麻素 建立SAR规则。 根据初步工作，我们希望能够 为了表明可以在大麻和 抗神性活性。 iv。 我们的小组和S. Bustein的工作 表明大麻和刻度活性之间的分离是 可能的。 我们计划制备化合物，主要是两种类型（大麻素 - 大麻二酚类型化合物的7-烯酸和单烷基醚） 哪些初步适应性为分离活动。 V.我们 已经表明（+） - 7-OH-DELTA6-THC DIMETHYLHEPTY同源物（HU-211）块 吗啡的呼吸抑郁症。 我们计划扩大我们的研究 区域并寻找类似的镇痛作用的鸦片活性阻断 胃肠道活动。