| 15094514 |
Reddy DS: Anticonvulsant activity of the testosterone-derived neurosteroid 3alpha-androstanediol. Neuroreport. 2004 Mar 1;15(3):515-8.
3alpha-Androstanediol is synthesized from testosterone in peripheral tissues and in the brain, but the clinical importance of this neurosteroid remains unclear. This study evaluated the effects of 3alpha-androstanediol on seizure susceptibility in mouse models of epilepsy. 3alpha-Androstanediol protected mice against seizures induced by GABAA receptor antagonists pentylenetetrazol, picrotoxin, and beta-carboline ester in a dose-dependent fashion. However, 3alpha-androstanediol was inactive against seizures induced by glutamate receptor agonists kainic acid, NMDA and 4-aminopyridine. Pretreatment with the androgen receptor antagonist flutamide had no effect on seizure protection by 3alpha-androstanediol. These results suggest that 3alpha-androstanediol has powerful anticonvulsant activity that occurs largely through non-genomic mechanisms. Testosterone-derived 3alpha-androstanediol might be an endogenous protective neurosteroid in the brain. |
81(1,1,1,1) |