CHARACTERIZATION OF CENTRAL SEROTONERGIC RECEPTORS

拟议项目的目标是描述 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。这其中的一部分 涉及使用体外结合分析，其使用的配体包括 ~3H-5-羟色胺和~3H-酮丝氨酸，它们被认为是标记特定人群的 5-羟色胺受体。这项工作的一个主要重点将是 这些受体的药理学特征以确定 区分不同种类化合物的结构要求 5-羟色胺受体的类型。结合配基结合分析，A 将开展新化合物合成计划。因此， 来自结合分析的信息将用于设计新的 用于测试5-羟色胺受体的化合物。该项目的另一部分将 是功能性5-羟色胺受体的特性，在体外和体内 活着。这将包括检查5-羟色胺受体，它介导 大鼠脑血管和眼底的收缩及检查 中枢5-羟色胺受体参与控制呼吸、血液 压力、体温和某些脑下垂体激素的释放，如 如催乳素和促甲状腺激素。功能性受体的研究将 提供关于化合物是激动剂还是拮抗剂的信息 5-羟色胺和功能性受体的特性是否相关 与通过配基结合测定的推定受体的同源性。和以前一样 配体结合研究，这是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。一旦这些 对受体组进行了分类和表征，希望能有更多 可以设计特定的药物，这将有助于研究这些作用 5-羟色胺在中枢神经系统的作用。希望来自这样的信息 研究可用于设计新的、更有效的治疗方法 用于治疗被认为是行为或精神障碍的药物 与中枢神经5-羟色胺能功能异常有关 系统。

The objective of the proposed project is the characterization of the properties of the different types of serotonin (5-hydroxytryptamine, 5-HT) receptors in the mammalian central nervous system (CNS). One part of this involves the use of in vitro binding assays utilizing ligands such as 3H-5-HT and 3H-ketanserin, which are thought to label specific populations of serotonin receptors. A major emphasis of this work will be the pharmacological characterization of these receptors to determine the structural requirements of compounds for discrimination between different types of 5-HT receptors. In conjunction with the ligand-binding assays a program for the synthesis of new compounds will be carried out. Thus, information from the binding assays will be used for the design of new compounds for testing at 5-HT receptors. Another part of the project will be the characterization of functional 5-HT receptors, both in vitro and in vivo. This will include examination of 5-HT receptors which mediate contraction of the cerebral vasculature and the rat fundus and examination of central 5-HT receptors involved in the control of respiration, blood pressure, body temperature, and release of certain pituitary hormones such as prolactin and thyrotropin. The study of functional receptors will provide information as to whether the compounds are agonists or antagonists of 5-HT 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 these groups of receptors are classified and characterized, it is hoped that more specific drugs can be designed which 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 behavioral or mental disorders that are thought to be linked to abnormal serotonergic function in the central nervous system.