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1. The pioneering work of Hans Selye over 50 years ago demonstrated that certain steroid metabolites can produce a rapid depression of central nervous system activity. 2. Research during the last 10 years has established that such effects are mediated by a nongenomic and specific interaction of these steroids with the brain's major inhibitory receptor, the GABAA receptor. 3. Here we describe the molecular mechanism of action of such steroids and review attempts to define the steroid binding site on the receptor protein. The therapeutic potential of such neurosteroids is discussed.
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