NEUROPHARMACOLOGY OF CONVULSANTS AND ANTICONVULSANTS

这是一个建议，以表征分子机制和网站的行动 新发现的神经活性丁内酯的神经学作用 和相关化合物。这个项目将测试假设，这些 化合物在神经系统中具有高度特异性的位点和作用机制， 组织，负责控制特定的神经功能， 并且具有开发为治疗以下疾病的有用药物的潜力： 一些神经系统疾病 该项目的目标与上述三个项目的目标相辅相成。 方案项目“基本机制”的其他组成部分 癫痫" 我们的具体目标是： (1)为了充分表征惊厥药、抗惊厥药和其他 几种丁内酯和相关化合物的神经学作用 实验动物（大鼠和小鼠）的行为研究。我们将比较 这些化合物与其他已知药物的神经学作用 调节大脑神经元的兴奋性。 (2)识别、表征并可能定位介导 神经活性丁内酯和相关化合物的作用 大鼠和小鼠脑组织膜的受体结合研究。我们 将明确丁内酯受体-配体的作用机制和性质 相互作用和表征GABA之间的相互作用过程， 苯并二氮卓和丁内酯受体。 (3)描述丁内酯的时间发展特征 受体和神经活动在出生后的成熟。 (4)试图确定神经活性丁内酯和相关的 神经疾病的病理生理机制中的化合物， 通过确定丁内酯的作用和/或作用是否 在动物和人类的脑组织中改变， 疾病或失调。 上述研究的医学意义是显而易见的。我们认为 获得上述信息将有助于我们识别 具有高治疗潜力的化合物，特别是可以 更有效和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， 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.