Anticonvulsant activity of the testosterone-derived neurosteroid 3alpha-androstanediol. Academic Article

abstract

• 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.

authors

• Reddy, Samba

published proceedings

• Neuroreport

altmetric score

• 3

author list (cited authors)

• Reddy, D. S.

citation count

• 60

complete list of authors

• Reddy, Doodipala S

publication date

• January 2004

publisher

• Wolters Kluwer  Publisher

published in

• NeuroReport  Journal

keywords

• Androgen Antagonists
• Androstane-3,17-diol
• Animals
• Anticonvulsants
• Carbolines
• Convulsants
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Agonists
• Flutamide
• Male
• Mice
• Mice, Inbred C57BL
• Pentylenetetrazole
• Picrotoxin
• Receptors, Androgen
• Receptors, GABA-A
• Seizures
• Testosterone

Digital Object Identifier (DOI)

• 10.1097/00001756-200403010-00026

start page

• 515

end page

• 518

volume

• 15

issue

• 3

URL

• http://dx.doi.org/10.1097/00001756-200403010-00026