CHARACTERIZATION OF CENTRAL SEROTONERGIC RECEPTORS

该项目的目标是研究其药理特性。 不同类型5-羟色胺(5-羟色胺)的性质 哺乳动物中枢神经系统中的受体。再加上这个 是一个设计和合成新化合物的程序，旨在努力 开发更有效和更具选择性的5-羟色胺能激动剂和拮抗剂 用作研究含5-羟色胺的功能作用的工具 神经元。三大类化合物的广泛系列 将对结构进行检查。这些药物包括吲哚胺类似物。 (四氢吡啶烷和芳基取代色胺)，螺沙碱 类似物和氨基四氢呋喃衍生物。世界上最重要的一部分 受体的表征和新化合物的筛选将 涉及使用放射性配基结合技术来测量以下内容 中枢性5-羟色胺受体亚型：5-HT1A、5-HT1B、5-HT1C和5-HT2。 该项目的另一部分将是功能性5-羟色胺的表征 体外和体内的受体。特别有趣的是大脑 血管系统，与外周血管系统不同，它似乎接收到 中枢性5-羟色胺能神经元的神经支配及其与5-HT1a的关系 感受器。更多的功能研究将检查 5-羟色胺调节体温的化合物和5-羟色胺 综合症。对功能性5-羟色胺受体的研究将提供信息 关于化合物是激动剂、拮抗剂还是部分激动剂 以及功能性受体的特性是否与这些相关 通过配基结合测定的推定受体。就像 配体结合研究，该项目这一部分的主要重点 将尝试确定化合物的结构要求 用于区分不同类型的5-羟色胺受体。一旦 对这些受体的性质进行了表征，希望 可以设计更具选择性的药物，以促进对 5-羟色胺在中枢神经系统中的作用和作用希望来自中国的信息 这样的研究可以用于设计新的、更有效的治疗方法 用于治疗生理和精神障碍的药物 被认为与中枢5-羟色胺能功能异常有关 神经系统。

The objective of the project is the pharmacologic characterization of the properties of the different types of serotonin (5-hydroxytryptamine, 5-HT) receptors in the mammalian central nervous system (CNS). Coupled with this is a program for the design and systhesis of new compounds in an effort to develop more potent and selective serotonergic agonists and antagonists to use as tools for the study of the functional roles of 5-HT-containing neurons. Extensive series of compounds in three major classes of structures will be examined. These include indoleamine analogs (tetrahydropyridylinodoles and arylsubstituted tryptamines), spiroxatrine analogs, and aminotetralin derivatives. A major part of the characterization of the receptors and screening of new compounds will involve the use of radioligand-binding techniques to measure the following subtypes of central 5-HT receptors: 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2. Another part of the project will be the characterization of functional 5-HT receptors both in vitro and in vivo. Of special interest is the cerebral vasculature, which unlike the peripheral vasculature appears to receive innervation from central serotonergic neurons and to contain 5-HT1A receptors. Additional functional studies will examine the actions of the compounds at 5-HT-modulated temperature regulation and in the serotonin syndrome. The study of functional 5-HT receptors will provide information as to whether the compounds are agonists, antagonists, or partial agonists and whether the properties of the functional receptors correlate with those of the putative receptors measured by ligand-binding. As with the ligand-binding studies, a major emphasis of this portion of the project will be the attempt to determine the structural requirements of compounds for discrimination between different types of 5-HT receptors. Once the properties of these groups of receptors are characterized, it is hoped that more selective drugs can be designed that will facilitate the study of the roles and actions of 5-HT in the CNS. It is hoped that information from such studies can be used for the design of new, more effective therapeutic agents for the treatment of physiologic and mental disorders that are thought to be linked to abnormal serotonergic function in the central nervous system.