COCAINE--A STUDY OF THE BIOCHEMICAL MECHANISM OF ACTION

可卡因是一种精神运动刺激剂，具有奖励或 “加固”财产。相关的药理作用 关于奖励和滥用责任，有一节是关于 多巴胺能突触。可卡因延长脑组织的活性 通过阻断多巴胺受体在突触中的多巴胺 机制。 可卡因和类可卡因药物对自身的效力 管理研究与它们在抑制中的效力相关 ~3H-马吲哚与大鼠多巴胺摄取部位的结合 纹状体。由于不存在绑定到大型 可卡因的其他突触前和突触后结合部位的数量 与物质滥用相关的受体似乎是 与多巴胺摄取抑制有关。 在这项研究中，设计、合成和受体结合评价 作为研究可卡因类似物的一种方法 可卡因滥用责任的生化机制。分子 模拟研究用来研究构象 可卡因可能的药效团结合模式的能量学研究 并设计可卡因类似物以供研究。 由于独特的结构和立体化学要求 在生物系统中是由于互补的三个- 药物与其受体部位之间的空间相互作用 这些要求的实验确定可以用来 制作一张受体的图片。此信息将提供 新的和独特的生化研究工具，可以翻译成 成为治疗可卡因成瘾的新药物。

Cocaine is a psychomotor stimulant with rewarding or "reinforcing" property. The pharmacological effect responsible for the rewarding and hence the abuse liability is an section on the dopamenergic synapses. Cocaine prolongs the activity of dopamine in the synapse by blocking the dopamine receptor mechanism. The potency of cocaine and cocaine-like drugs in self- administration studies correlates with their potencies in inhibiting 3H-mazindol binding to the dopamine uptake site in the rat striatum. Since there is no correlation for binding to a large number of other pre-and post-synaptic binding sites the cocaine receptor related to substance abuse appears to be the one associated with dopamine uptake inhibition. In this study the design, synthesis and receptor binding evaluation of cocaine analogs are proposed as a method of investigating the biochemical mechanism of cocaine abuse liability. Molecular modeling studies were used to investigate the conformational energetics of possible pharmacophore binding modes for cocaine and to design the cocaine analogs proposed for study. Since the unique structural and stereochemical requirements seen in biological systems are due to a complementary three- dimensional interaction between a drug and its receptor site, the experimental determination of these requirements can be used to construct a picture of the receptor. This information will provide new and unique tools for biochemical studies and could translate into new agents for the treatment of cocaine addiction.