NEW PHARMACOLOGICAL TOOLS FOR ALPHA ADRENERGIC RECEPTORS

α 肾上腺素能受体的新药理学工具

• 批准号: 2272230
• 负责人: JOHN M WETZEL
• 金额: $ 7.5万
• 依托单位: SYNAPTIC PHARMACEUTICAL CORPORATION
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-15 至 1995-03-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2272230
• 关键词: affinity labeling; alpha adrenergic agent; alpha adrenergic receptor; alpha antiadrenergic agent; analgesia; autoradiography; benign prostate hyperplasia; drug design /synthesis /production; high performance liquid chromatography; human tissue; laboratory rat; ligands; neuropharmacology; protein isoforms; protein structure function; radiotracer; receptor binding; receptor expression

Alpha adrenoceptors serve numerous functions throughout the peripheral and central nervous systems. Chemical modulators of these receptors have a variety of potential therapeutic applications, including treatments for benign prostatic hyperplasia, hypertension, pain and glaucoma. Although six alpha adrenoceptor subtypes are now known, little information is available concerning the locations and physiological functions of these subtypes in the body. The three-dimensional structures of these receptors, and the chemical nature of their interactions with ligands are also poorly understood. Ligands were identified by our cloned human receptor screening program which bind selectively to individual alpha adrenoceptor subtypes. In Phase I, some of these compounds will be used as templates for the design of new pharmacological tools. These tools will include molecules that selectively inactivate one subtype by covalent modification, as well as subtype-selective radioligands. In Phase I and II, these new pharmacological tools will be used to determine the localization and functional capabilities of the different alpha adrenergic subtypes in various human and animal tissues. These tools will also be useful for structural characterization of the receptor-ligand complexes. Information obtained in these studies will aid the identification of new therapeutic opportunities and the design of new drugs.

在整个周围和 中枢神经系统。这些受体的化学调节剂具有 各种潜在的治疗应用，包括 良性前列腺增生，高血压，疼痛和青光眼。 尽管现在已知六个alpha adrenoceptor子类型，但信息很少 有关这些位置和生理功能的可用 体内的亚型。这些受体的三维结构， 它们与配体相互作用的化学性质也很差 理解。 配体通过我们的克隆人类受体筛选程序鉴定 它与单个α肾上腺肾上腺类的亚型有选择地结合。在阶段 我，其中一些化合物将用作新设计的模板 药理工具。 这些工具将包括分子 通过共价修改有选择地使一种亚型失活，以及 亚型选择性放射线。 在第一阶段和第二阶段，这些新的药理学工具将用于 确定不同的本地化和功能功能 各种人类和动物组织中的α肾上腺素亚型。这些工具 也将有助于受体配体的结构表征 复合物。在这些研究中获得的信息将有助于 确定新的治疗机会和新的设计 毒品。