CHARACTERIZATION OF CENTRAL SEROTONERGIC RECEPTORS

该项目的目的是药理学表征的 不同类型血清素（5-羟色胺，5-HT）的性质 哺乳动物中枢神经系统（CNS）中的受体。 再加上这 是一个设计和合成新化合物的程序， 开发更有效和选择性的肾上腺素能激动剂和拮抗剂， 用作研究含5-HT的 神经元 三大类化合物的广泛系列 将对结构进行检查。 这些包括吲哚胺类似物 （四氢吡啶吲哚和芳基取代的色胺），螺沙嘌呤 类似物和氨基四氢化萘衍生物。 的主要部分 受体的表征和新化合物的筛选将 涉及使用放射性配体结合技术来测量以下 中枢5-HT受体亚型：5-HT 1A、5-HT 1B、5-HT 1C和5-HT 2。 该项目的另一部分将是功能性5-HT的表征 受体在体外和体内。 特别感兴趣的是大脑 与外周血管系统不同， 来自中枢多巴胺能神经元的神经支配和含有5-HT 1A 受体。 其他功能研究将检查 化合物在5-HT调节的温度调节和血清素 综合征 对5-HT受体功能的研究将为临床应用提供信息 至于化合物是激动剂、拮抗剂还是部分激动剂 以及功能性受体的特性是否与那些 通过配体结合测量的推定受体。 如同 配体结合研究，该项目这一部分的主要重点 将试图确定化合物的结构要求 用于区分不同类型的5-HT受体。 一旦 表征了这些受体组的性质，希望 可以设计出更有选择性的药物，这将有助于研究 5-HT在中枢神经系统中的作用。 希望来自 这些研究可用于设计新的、更有效的治疗方法， 用于治疗生理和精神障碍的药物， 被认为与中枢神经系统的异常多巴胺能功能有关 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.