Neurosteroids and infantile spasms: the deoxycorticosterone hypothesis.
作者： Michael A Rogawski , Doodipala S Reddy , None
DOI: 10.1016/S0074-7742(02)49014-9
关键词:
摘要: Deoxycorticosterone (DOC) is a mineralocorticoid precursor that has anticonvulsant properties in animals and possibly also humans. Studies indicate the activity of DOC requires its enzymatic conversion to 5 alpha,3 alpha-tetrahydrodeoxycorticosterone (THDOC), neurosteroid lacks classical hormonal but acts as powerful positive allosteric modulator GABAA receptors. can be considered stress hormone because synthesis under control ACTH. Therefore, stress-induced fluctuations seizure susceptibility could part result from alterations availability. Also, therapeutic ACTH infantile spasms partially relate stimulatory effects on DOC, which then undergoes biotransformation neurosteroids. The recent demonstration synthetic analog ganaxolone reduces spasm frequency children with intractable suggests neurosteroid-related anticonvulsants may offer potential new nonhormonal approach for treatment other developmental epilepsies. In addition, it further confirms utility pharmacological enhancement GABA-mediated inhibition spasms.
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