ANESTHETICS--CELLULAR AND MOLECULAR ACTIONS

全麻药在临床上的作用机制 人们并不了解预期的效果。报告中提出的工作 该计划旨在定义这些药物的分子靶点(S)，并 阐明在这些靶点上的作用导致麻醉的方式。 其基本思想是麻醉剂在蛋白质的特定位置起作用。 尤其是，参与地层转移的蛋白质 神经元。该计划的一个主要重点是了解 类固醇麻醉药的性质，作为研究进展的结果 前面的课程是了解类固醇的性质 麻醉药，作为前一计划期间进展的结果。 该计划的一个目标是确定类固醇的作用 几类膜通道上的麻醉药，包括GABA- A受体、谷氨酸能受体、神经元烟碱受体和 电压门控钙通道。该计划的第二个目标是 定义类固醇与On特异性相互作用的结构基础 靶点是GABA-A受体。这些研究将涉及 甾体类似物结构与分子的互补研究 重组受体亚单位的操纵。照片激活站点 还将开发类固醇结合位点的特定探针。这个 该方案的第三个目标是描述下列机制 类固醇麻醉剂对靶点有影响。决赛 目的是将药理结果与生产 麻醉或其他仅在整个动物水平上定义的状态。 尽管总体重点是麻醉剂类固醇，但该计划将 包括检查额外的麻醉药，以便与 类固醇。然后，每个项目都解决了 麻醉药物在细胞和分子水平上的作用。这个 计划作为一个整体将整合这些互补的研究，并且 将它们与行为状态联系起来。

The mechanisms by which general anesthetics have their clinically desired effects are not understood. The work proposed in the Program seeks to define the molecular target(s) for these drugs, and to clarify the way in which action at these targets results in anesthesia. The underlying idea is that anesthetics act at defined sites on proteins and , in particular, the proteins involved in formation transfer between neurons. A major emphasis of the Program is to understand the properties of steroid anesthetics, as a result of progress in the preceding Program is to understand the properties of steroid anesthetics, as a result of progress in the preceding Program period. One objective of the Program is to define the actions of steroid anesthetics on several classes of membrane channel, including GABA- A receptors, glutamatergic receptors, neuronal nicotinic receptors and voltage-gate calcium channels. The second objective of the Program is to define the structural basis for steroid interaction with on specific target, the GABA-A receptor. These studies will involve complementary studies of steroid analogue structure and molecular manipulation of recombinant receptor subunits. Photo-activated site specific probes for steroid binding sites will also be developed. The third objective of the Program is to delineate the mechanisms by which steroid anesthetics have their effects on their targets. The final objective is to correlate pharmacological results with production of anesthesia or other states defined only at the whole animal level. Although the overall focus is on anesthetic steroids, the program will include examination of additional anesthetics for comparison to the steroids. Each project, then, addresses on or another aspect of the action of anesthetic drugs at the cellular and molecular level. The Program as a whole will integrate these complementary studies, and relate them to behavioral states.