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

目前，没有药物可供患有以下疾病的患者使用 中度至重度疼痛，有以下特征：无身体症状 药物依赖倾向，很少或没有口服或过量致命性，很少 或对呼吸中枢无影响，口服有效，长效。在……里面 这个项目我们建议准备和药物学评估六个 Delta9-四氢大麻酚(THC)的含氮类似物，包括两个 水溶性衍生品。这些化合物的设计和仿制 Cannabis Sativa的活跃主体是因为THC是相对独特的 作用于中枢神经系统(CNS)的药物中。天然产物 THC是独一无二的，因为(A)它们的 分子结构；(B)在下列情况下，它们不会对实验动物致命 口服；。(C)对呼吸系统几乎没有影响；及。 (D)尽管它们表现出明显的中枢神经系统和一些心血管作用 (快感和心动过速)，大麻和THC从来都不是 据报道会导致身体上瘾或致死，尽管几个世纪以来 天然产物的使用和滥用。这些研究的初步结果 实验室(10名患者)与相关氮类似物的双盲试验 交叉相对效力分析在癌症术后疼痛中的应用 已经显示出缓解疼痛的效果，其效力是可待因的六倍。 经过二十年对普通化学、药理学的研究 及其衍生的新化学物质的结构活性 大麻核，这是本项目的具体目标，以(1) 合成并研究详细的抗伤害性、药理学特性 四种精选的含苯乙胺的氮类似物 在类麻醉剂镇痛剂中发现的化学基团，以及(2)选择下列之一 这些用于后续的、深入的、第二阶段的资助和潜在的研究 有市场的独一无二的产品，用于术后疼痛，关节炎疼痛， 牙痛等老年疼痛模型。

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.