期刊
PHARMACOLOGY & THERAPEUTICS
卷 116, 期 1, 页码 35-57出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2007.03.004
关键词
GABA; neurosteroid; Anesthesia; enantiomer; electrophysiology; Photoaffinity label
资金
- NIAAA NIH HHS [R21 AA014707-01A2, AA12952, AA12951, R01 AA012952-01A1, R21 AA014707, AA14707, R01 AA012952, R01 AA012951, R01 AA012951-01A1] Funding Source: Medline
- NIA NIH HHS [P01 AG010485-149007] Funding Source: Medline
- NIGMS NIH HHS [P01 GM047969-060001, GM47969, P01 GM047969-060005, P01 GM047969-060006, P01 GM047969, P01 GM047969-060004, P01 GM047969-069003] Funding Source: Medline
- NIMH NIH HHS [R01 MH078823-05A2, MH78823, R01 MH078823] Funding Source: Medline
- NINDS NIH HHS [R01 NS054174, P30 NS057105-019006, NS54174, P30 NS057105, R01 NS054174-01A1] Funding Source: Medline
Neuroactive steroids have some of their most potent actions by augmenting the function of GABA(A) receptors. Endogenous steroid actions on GABAA 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 GABAA 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. (c) 2007 Elsevier Inc. All rights reserved.
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