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Full-Text Articles in Medical Neurobiology
Anticonvulsant Potencies Of The Enantiomers Of The Neurosteroids Androsterone And Etiocholanolone Exceed Those Of The Natural Forms, Dorota Zolkowska, Ashish Dhir, Kathiresan Krishnan, Douglas F. Covey, Michael A. Rogawski
Anticonvulsant Potencies Of The Enantiomers Of The Neurosteroids Androsterone And Etiocholanolone Exceed Those Of The Natural Forms, Dorota Zolkowska, Ashish Dhir, Kathiresan Krishnan, Douglas F. Covey, Michael A. Rogawski
Michael A. Rogawski
RATIONALE: Androsterone [(3α,5α)-3-hydroxyandrostan-17-one; 5α,3α-A] and its 5β-epimer etiocholanolone [(3α,5β)-3-hydroxyandrostan-17-one; 5β,3α-A)], the major excreted metabolites of testosterone, are neurosteroid positive modulators of GABA-A receptors. Such neurosteroids typically show enantioselectivity in which the natural form is more potent than the corresponding unnatural enantiomer. For 5α,3α-A and 5β,3α-A, the unnatural enantiomers are more potent at GABA-A receptors than the natural forms. OBJECTIVES: The aim of this study was to compare the anticonvulsant potencies and time courses of 5α,3α-A and 5β,3α-A with their enantiomers in mouse seizure models. METHODS: Steroids were administered intraperitoneally to male NIH Swiss mice 15 min (or up to 6 …