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In Vivo Studies Identify 5a‐Pregnan‐3a‐o1‐20‐one as an Active Anesthetic Agent
Author(s) -
Mok Wai Man,
Herschkowitz Sylvia,
Krieger Neil R.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb08293.x
Subject(s) - in vivo , anesthetic , anesthetic agent , chemistry , neuroscience , pharmacology , anesthesia , medicine , biology , genetics
Mice were anesthetized with 5a‐[ 3 H]pregnan‐3a‐o1‐20‐one. Brain levels for 5α‐pregnan‐3α‐o1–20‐one and its five major metabolites (5α‐pregnanedione, k o , k 1 , k 2 , k 3 ) were compared at behavioral endpoints that are characteristic of the anesthetized state. The results support the hypothesis that 5α‐pregnan‐3α‐o1–20‐one mediates the anesthetic response, and they weigh against the hypothesis that any of its metabolites is solely responsible for the onset or the maintenance of the anesthetized state. For an administered dose of 3 mg/kg, brain levels (means ± SEM) for 5α‐pregnan‐3α‐o1–20‐one at the time of the loss of the righting response (n = 10) and at the time of the return of the righting response (n = 6) were 7.24 ± 0.61 pmol/mg of brain tissue and 3.63 ± 0.26 pmol/mg of brain tissue, respectively. No metabolite level was lower at the return of the righting response than at the loss of the righting response. 5α‐Pregnan‐3′‐o1–20‐one brain levels increased consistently with the percentage of anesthetized mice. This was not the case for any of the metabolites. Fifty percent of the mice were anesthetized when the 5α‐pregnan‐3α‐o1–20‐one level was 4.5 pmol/mg of brain tissue.