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Neurosci Lett. 1992 Feb 3;135(2):145-8.

Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is the metabolite responsible for anesthesia induced by 5 alpha-pregnanedione in the mouse.

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  • 1Department of Anesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115.


Mice were anesthetized with [3H]5 alpha-pregnanedione (5 alpha). Brain levels for 5 alpha and its metabolites were quantitated and compared at time points following injection and at two behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha), a metabolite of 5 alpha, mediates this anesthetic response, and they weigh against the hypothesis that 5 alpha itself is solely responsible for activity. Anesthesia occurred at 3-8 min following injection. During this period, levels of 3 alpha derived from 5 alpha were comparable to those seen when 3 alpha was administered alone. It is estimated that 5 alpha, if active at all, is at least 3-5 times less potent than 3 alpha.

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