CHARACTERIZATION OF CENTRAL SEROTONERGIC RECEPTORS

拟议项目的目标是描述 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。 其中一部分 涉及使用体外结合测定， [H-3]5-HT、[H-3]PAT和[H-3] ketsanserin，它们被认为是标记 5-羟色胺受体的特定群体。 这项工作的主要重点是 将是这些受体的药理学特征， 确定化合物的结构要求以进行区分 不同类型的5-HT受体之间的联系。 联同 配体结合分析新化合物的合成程序将 贯彻 因此，来自结合测定的信息将用于本发明。 设计新的化合物用于5-HT受体的测试。 的另一部分 项目将是功能性5-HT受体的表征，无论是在 体外和体内。 这将包括检查5-HT受体， 介导脑血管和5-HT自身受体的收缩， 调节5-HT的释放，以及对中枢5-HT的检测 参与呼吸、血压、身体控制的受体 温度和某些垂体激素的释放，如催乳素 和促甲状腺激素。 对功能性受体的研究将提供 关于化合物是5-HT的激动剂还是拮抗剂的信息 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。 一旦这些 受体的分类和特点，这是希望更多 可以设计特定的药物，这将有助于研究 以及5-HT在中枢神经系统中的作用。 希望这些信息 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 与中枢神经系统中的肾上腺素能功能异常有关 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 [H-3]5-HT, [H-3]PAT, and [H-3] ketsanserin, 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 form the binding assays will be used in 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 that mediate contraction of the cerebral vasculature and 5-HT autoreceptors that regulate the release of 5-HT, as well as 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 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 behavioral or mental disorders that are thought to be linked to abnormal serotonergic function in the central nervous system.