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  • Title: 5 beta-pregnan-3 beta-ol-20-one, a specific antagonist at the neurosteroid site of the GABAA receptor-complex.
    Author: Prince RJ, Simmonds MA.
    Journal: Neurosci Lett; 1992 Feb 03; 135(2):273-5. PubMed ID: 1320747.
    Abstract:
    Studies were made on the potentiation of [3H]flunitrazepam binding to rat brain membranes by gamma-aminobutyric acid (GABA), pentobarbitone and pregnanolone (5 beta-pregnan-3 alpha-ol-20-one). Epipregnanolone, the 3 beta isomer of pregnanolone, inhibited competitively the potentiation by pregnanolone with a Ki of 10.5 microM without affecting that of GABA. The potentiation by pentobarbitone was slightly enhanced. Epipregnanolone alone showed only slight potentiation of benzodiazepine binding. These findings demonstrate that epipregnanolone is a specific antagonist of the neurosteroid site of the GABAA receptor and raise the possibility of a physiological role for 3 beta-hydroxysteroids in modulating this receptor.
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