PHASE II: DEVELOPMENT OF MENABITAN, A NOVEL ANALGESIC (1

目前，没有药物可供患者使用。 中度至重度疼痛，具有以下特征：无身体 药物依赖倾向，很少或没有口服或过量致死性，很少 或对呼吸中枢无影响，口服有效，长效。 在 本项目我们建议准备和药理学评估六个 δ 9-四氢大麻酚（THC）的氮类似物，包括两个 水溶性衍生物。 这些化合物是根据 因为THC相对独特 在作用于中枢神经系统（CNS）的药物中。 天然产物 四氢大麻酚是独特的，因为（a）它们在它们的分子中不含元素氮， 分子结构;（B）当 （c）它们显示很少或没有呼吸作用;和 (d)尽管它们表现出明显的中枢神经系统和一些心血管效应 （欣快症和心动过速），大麻和THC都没有 据报道，尽管有几个世纪的历史， 天然产品的使用和滥用。 初步结果显示， 实验室（10名患者）与相关的氮类似物在双盲 交叉相对效力测定在癌症术后疼痛中的应用， 止痛效果是可待因的六倍 经过20年的普通化学、药理学研究， 新化学物质的结构和活性 大麻素核，这是本项目的具体目标（1） 合成和研究详细的抗伤害性，药理学特征 四个精心挑选的氮类似物， 在麻醉类镇痛药中发现的化学成分，以及（2）选择其中一种 这些后续，深入，第二阶段的资金和研究，作为一个潜在的 用于手术后疼痛，关节炎疼痛， 牙疼等老年人疼痛模型。

At the present time there is no medication available to patients with moderate to severe pain with the following characteristics: No physical drug dependence liability, little or no oral or overdose lethality, little or no effects on respiratory centers, orally potent, and long acting. In this project we propose to prepare and pharamacologically evaluate six nitrogen analogs of Delta9-Tetrahydrocannabinols (THC's) including two water soluble derivatives. These compounds are designed and modeled after the active principal of Cannabis Sativa because THC's are relatively unique among drugs acting on the central nervous system (CNS). Natural products THC's are unique because (a) they contain no elemental nitrogen in their molecular structures; (b) they are not lethal to laboratory animals when administered orally; (c) they show little or no respiratory effects; and (d) though they exhibit marked CNS and some cardiovascular effects (euphoria and tachycardia), neither cannabis nor THC's have ever been reported to result in physical addiction or lethality, despite centuries of use and abuse of the natural product. Preliminary results from these laboratories (10 patients) with a related nitrogen analog in a double blind crossover relative potency assay in post-operative pain due to cancer, has already shown pain relief which is six times the potency of codeine. Following twenty years of research on the general chemistry, pharmacology and structure activity of new chemical substances derived from the cannabinoid nucleus, it is the specific aim of this project to (1) synthesize and study the detailed anti-nociceptive, pharmacological profile of four carefully selected nitrogen analogs having phenylethyl amine chemical moities found in narcotic-like analgesics, and (2) choose one of these for follow-on, in-depth, Phase II funding and study as a potentially marketable unique product for use in post-operative pain, arthritic pain, dental pain and other pain models for the aged.