Akk Gustav, Covey Douglas F, Evers Alex S, Steinbach Joe Henry, Zorumski Charles F, Mennerick Steven
Department of Anesthesiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, United States.
Pharmacol Ther. 2007 Oct;116(1):35-57. doi: 10.1016/j.pharmthera.2007.03.004. Epub 2007 Apr 20.
Neuroactive steroids have some of their most potent actions by augmenting the function of GABA(A) receptors. Endogenous steroid actions on GABA(A) receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABA(A) receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.
神经活性甾体通过增强GABA(A)受体的功能发挥其一些最有效的作用。内源性甾体对GABA(A)受体的作用可能是对情绪和行为产生重要影响的基础。外源性神经活性甾体有作为麻醉剂、抗惊厥药和神经保护剂的潜力。我们采用了多种方法来更全面地了解神经活性甾体与GABA(A)受体的相互作用。为此我们已研发出许多新型甾体类似物。最近的工作已合成了新的对映体类似物对、用于探究甾体药效基团各种特性的新型配体、荧光神经活性甾体类似物以及光亲和标记物。利用这些工具，结合受体结合和电生理测定，我们已开始梳理这类重要的配体门控离子通道上甾体作用的复杂性。
