NEUROPHARMACOLOGY OF CONVULSANTS AND ANTICONVULSANTS

这是一项描述分子机制和作用部位的提议。 以及新发现的神经活性丁内酯的神经学效应 以及相关化合物。这个项目将检验这样的假设： 化合物在神经细胞中具有高度特异性的作用部位和作用机制 组织负责控制特定的神经功能， 并有潜力开发为治疗该病的有用药物 一些神经紊乱。 这个项目的目标与三个项目的目标是相辅相成的。 项目“基本机制”项目的其他组成部分 癫痫发作。“ 我们的具体目标是： (1)全面描述惊厥、抗惊厥等 几种丁内酯及其相关化合物的神经学效应 实验动物(大鼠和小鼠)的行为研究。我们会比较一下 这些化合物与其他已知药物的神经学效应 调节大脑中神经元的兴奋性。 (2)鉴定、鉴定和可能定位介导的受体 神经活性丁内酯及其相关化合物的作用 大鼠和小鼠脑组织膜的受体结合研究。我们 将确定丁内酯受体-配体的作用机制和性质 相互作用并描述GABA之间相互作用过程， 苯二氮卓类和丁内酯受体。 (3)丁内酯的时间发展特征 受体和神经在出生后成熟过程中的作用。 (4)试图明确神经活性丁内酯及其相关物质的作用 神经疾病的病理生理机制中的化合物和 通过确定丁内酯效应和/或行为是否 在已知神经学疾病的动物和人类的脑组织中发生改变 疾病或紊乱。 上述研究的医学意义似乎是显而易见的。我们相信 获得上述信息将有助于我们确定 具有高治疗潜力的化合物，特别是可能 更有效且毒性更低的抗惊厥药，抗焦虑药， 镇静剂/催眠药，也许还有兴奋剂和认知增强剂，比 目前可用的药物。

This is a proposal to characterize molecular mechanisms and sites of action and neurologic effects of the newly discovered neuroactive butyrolactones and related compounds. This project will test the hypothesis that these compounds have highly specific sites and mechanisms of action in nervous tissue, are responsible for controlling specific neurological functions, and have the potential for development as useful drugs for the treatment of some neurologic disorders. The objectives of this project are complementary with those of the three other component components of the program project "Basic Mechanisms of Seizures." Our specific objectives are: (1) To fully characterize the convulsant, anticonvulsant, and other neurologic effects of several butyrolactones and related compounds using behavioral studies of experimental animals (rats and mice). We will compare the neurologic effects of these compounds with other drugs which are known to regulate neuronal excitability in brain. (2) To identify, characterize and possibly locate the receptors mediating the action of neuroactive butyrolactones and related compounds using receptor binding studies of brain tissue membranes from rats and mice. We will define the mechanism and character of butyrolactone receptor-ligand interaction and characterize interactive processes among the GABA, benzodiazepine and butyrolactone receptors. (3) To characterize the chronological development of butyrolactone receptors and neurologic actions during postnatal maturation. (4) To attempt to define the role of neuroactive butyrolactones and related compounds in pathophysiologic mechanisms of neurological diseases and disorders by determining whether butyrolactone effects and/or actions are altered in brain tissue from animals and humans with known neurological diseases or disorders. The medical significance of the above studies seems obvious. We believe that obtaining the information described above will help us identify compounds with high therapeutic potential, particularly agents that may be more effective and less toxic anticonvulsants, anxiolytics, sedative/hypnotics and, perhaps, stimulants and cognitive enhancers, than presently available drugs.