ORALLY ACTIVE AND SELECTIVE ENKEPHALIN PSEUDOPEPTIDES

越来越多的证据表明，突触后5-羟色胺（5-HT）受体是 致幻药物的重要作用部位 同时，在 近年来，5-HT在脑和外周的结合位点的研究越来越多。 这些地点被分为三大类，最常见的是 称为5-HT 1、2和3。 5-HT 1位点已被进一步 分为5-HT 1A、1B、1C和1D。 当前的总体目标 建议是表征的电生理行动， 突触后5-HT受体介导的致幻剂及相关药物 中缝核能神经元 被测试的致幻剂包括麦角 D-LSD、吲哚类裸盖菇素和N，N-二甲基色胺，以及 苯基烷基胺美斯卡灵和2，5-二甲氧基-4-甲基安非他明。 他们的 将与那些可能非致幻剂的作用进行比较， 包括5-HT、5-羧酰胺色胺、麦角脲和2-溴麦角酸 酸二乙基酰胺 多巴胺对5-HT兴奋性作用的调节 致幻剂也将受到调查。 电生理实验 （场电位记录和细胞内和细胞外单位 研究）将在体外对大鼠海马切片进行。 的 致幻剂的作用将在海马CA 1区进行表征 以及与其效力相比的电生理效应， 对与膜中腺苷酸环化酶连接的两种5-HT受体的效力 形成大鼠海马。 腺苷酸环化酶的抑制将是 评估。 LSD与所有5-HT 1和5-HT 2位点结合。 地区 海马结构显示5-HT 1B、5-HT 1C密度最高 和5-HT 2的网站将进行检查，以确定是否电生理 作用可以与这些部位的药物作用相联系。 可能的联系 5-HT 1B位点对腺苷酸环化酶的影响。 这些 研究应该提供一些关于多巴胺能作用机制的信息， 在海马体和受体及效应器上 它们的作用是通过这些物质来介导的。

Evidence has accumulated that postsynaptic serotonin (5-HT) receptors are an important site of action for hallucinogenic drugs. Concomitantly, there has been intensive study of 5-HT binding sites in brain and periphery. These sites have been classified into three main groups, most commonly referred to as 5-HT 1, 2 and 3. The 5-HT 1 sites have been further subdivided into 5-HT 1A, 1B, 1C and 1D. The overall goal of the present proposal is to characterize the electrophsiological actions of hallucinogens and related drugs mediated by 5-HT receptors postsynaptic to serotonergic raphe neurons. Hallucinogens to be tested include the ergot D-LSD, the indoles psilocin and N,N-dimeth-yltryptamine, and the phenylalkylamines mescaline and 2,5-dimethoxy-4-methylamphetamine. Their actions will be compared with those of presumably non-hallucinogenic agents including 5-HT, 5-carboxyamidotryptamine, lisuride, and 2-bromolysergic acid diethylamide. Modulation of excitatory actions of 5-HT by hallucinogens will also be investigated. Electrophysiological experiments (field potential recordings and both intracellular and extracellular unit studies) will be performed on the rat hippocampal slice in vitro. The actions of hallucinogens will be characterized in hippocampal field CA 1 and their electrophsiological effects compared with their potency and efficacy on the two 5-HT receptors linked to adenylate cyclase in membranes form rat hippocampus. The inhibition of adenylate cyclase will be assessed. LSD binds to all 5-HT 1 and 5-HT 2 sites. Regions of the hippocampal formation exhibiting the highest densities for 5-HT 1B, 5-HT 1C and 5-HT 2 sites will be examined to determine whether electophysiological effects can be linked to drug action at these sites. The possible linkage of the 5-HT 1B site to adenylate cyclase will be investigated. These studies should yield information on some serotonergic mechanisms of action of hallucinogens in the hippocampus and on the receptors and effectors through which their effects are mediated.