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Updated: Oct 11, 2025

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Neurosteroid Modulation of GABAA Receptor Function by Independent Action at Multiple Specific Binding Sites
Lei Wang1,2, Douglas F Covey1,3,4, Gustav Akk1,5
1Department of Anesthesiology (LW, DFC, GA, ASE),Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei , China.
Abstract:
Neurosteroids are endogenous modulators of GABAA receptors that mediate anxiety, pain, mood and arousal. The 3-hydroxyl epimers, allopregnanolone (3α-OH) and epiallopregnanolone (3β-OH) are both prevalent in the mammalian brain and produce opposite effects on GABAA receptor function, acting as positive and negative allosteric modulators, respectively. This Perspective provides a model to explain the actions of 3α-OH and 3β-OH neurosteroids. The model is based on evidence that the neurosteroid epimers bind to an overlapping subset of specific sites on GABAA receptors, with their net functional effect on channel gating being the sum of their independent effects at each site.
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