EXCITATORY AMINO ACIDS--ROLE IN CNS DISORDERS

该计划项目的长期目标是促进现有知识 兴奋性氨基酸（EAA）在CNS疾病中的作用， 这些知识作为开发新的药理学试剂的基础 有效治疗神经系统疾病。为了实现这一目标， 每个主要研究者将使用一套策略， 如下：（1）将寻求有关每个人角色的新信息 中枢神经系统疾病中EAA亚型。到目前为止，每种特定的EAA受体 亚型不能明确与特定的中枢神经系统功能或 功能障碍阐明NMDA、使君子酸和 红藻氨酸受体的特定功能和功能障碍将提供一个 新药开发的基础。(2)将要求提供新的资料， 士的宁不敏感甘氨酸受体在变构中的作用 NMDA受体的调节。专注于这种特殊的变构 调节位点是理解中枢神经系统的出发点 并用于开发新一代药物， 癫痫、肌肉痉挛、学习和记忆障碍 损伤、神经元死亡、脊髓创伤和脊髓疾病。 心血管和呼吸系统。(3)将寻求新的信息 EAA受体的信号转导机制。监管局的一个特点 受体是他们的能力，诱导形成多个 可以与其他传入刺激整合的细胞内信息 产生不同的神经元反应。中每个步骤的标识 细胞内信息的形成将有助于阐明 正常细胞功能和紊乱细胞功能的机制，以及 为开发药物提供基础， EAA受体。(4)将寻求关于其他机构的作用的新资料。 神经递质系统，可以调节大脑中的EAA系统， 脊髓我们假设监管局的制度可能受到 其他调节EAA传递或起作用的神经递质系统 独立地产生CNS病症。解释这些其他 发射器系统将为新药的开发提供基础， 或用于治疗神经障碍的药物组合。总的说来， 集中研究中枢神经系统功能障碍与特定EAA的关系 受体，侧步的主要识别位点，并集中在 NMDA受体复合物的调节位点，通过 着重于第二信使系统，并阐明其他 与EAA递质系统相互作用的神经递质系统提供了 设计新药以治疗各种疾病的机会 CNS疾病。

The long range goal of the program project is to advance current knowledge of the role of excitatory amino acids (EAA) in CNS disorders, and to use this knowledge as a basis for developing new pharmacological agents effective in the treatment of neurological disorders. To achieve this goal, a set of strategies will be used by each principal investigator and these are as follows: (1) New information will be sought on the role of each subtype of EAA in CNS disorders. As yet, each particular EAA receptor subtype cannot be clearly correlated with specific CNS functions or dysfunctions. Clarification of the relationship of NMDA, quisqualate and kainate receptors to specific functions and dysfunctions will provide one basis for new drug development. (2) New information will be sought on the role of the strychnine-insensitive glycine receptor in allosteric modulation of the NMDA receptor. Focusing on this specific allosteric modulatory site represents a point of departure for understanding CNS disorders and for the development of a new generation of drugs for disorders such as epilepsy, muscle spasticity, learning and memory impairments, neuronal death, spinal cord trauma, and diseases of the cardiovascular and respiratory system. (3) New information will be sought on the mechanism of signal transduction at EAA receptors. A feature of EAA receptors is their ability to induce the formation of multiple intracellular messages which may be integrated with other incoming stimuli to produce distinct neuronal responses. Identification of each step in the formation of intracellular messages will help elucidate molecular mechanisms for normal cell function and disordered cell function, and provide a basis for developing drugs that act one or several steps beyond the EAA receptor. (4) New information will be sought on the role of other neurotransmitter systems that can regulate the EAA systems in the brain and spinal cord. Our assumption is that the EAA system may be manipulated by other neurotransmitter systems that either regulate EAA transmission or act independently to produce CNS disorders. Elucidation of these other transmitter systems will provide a basis for the development of new drugs, or a combination of drugs for treating neurological disorders. In summary, concentration on relating disorders of CNS function to a specific EAA receptor, side stepping the primary recognition site and focusing on the modulator site of the NMDA receptor complex, bypassing the EAA receptor by focusing on second messenger systems, and elucidating other neurotransmitter systems that interact with EAA transmitter systems offer the opportunities for the design of new drugs to treat a wide spectrum of CNS disorders.