TY - JOUR
T1 - Neurosteroids as novel antidepressants and anxiolytics
T2 - GABA-A receptors and beyond
AU - Zorumski, Charles F.
AU - Paul, Steven M.
AU - Covey, Douglas F.
AU - Mennerick, Steven
N1 - Publisher Copyright:
© 2019 The Author(s)
PY - 2019/11
Y1 - 2019/11
N2 - The recent FDA approval of the neurosteroid, brexanolone (allopregnanolone), as a treatment for women with postpartum depression, and successful trials of a related neuroactive steroid, SGE-217, for men and women with major depressive disorder offer the hope of a new era in treating mood and anxiety disorders based on the potential of neurosteroids as modulators of brain function. This review considers potential mechanisms contributing to antidepressant and anxiolytic effects of allopregnanolone and other GABAergic neurosteroids focusing on their actions as positive allosteric modulators of GABAA receptors. We also consider their roles as endogenous “stress” modulators and possible additional mechanisms contributing to their therapeutic effects. We argue that further understanding of the molecular, cellular, network and psychiatric effects of neurosteroids offers the hope of further advances in the treatment of mood and anxiety disorders.
AB - The recent FDA approval of the neurosteroid, brexanolone (allopregnanolone), as a treatment for women with postpartum depression, and successful trials of a related neuroactive steroid, SGE-217, for men and women with major depressive disorder offer the hope of a new era in treating mood and anxiety disorders based on the potential of neurosteroids as modulators of brain function. This review considers potential mechanisms contributing to antidepressant and anxiolytic effects of allopregnanolone and other GABAergic neurosteroids focusing on their actions as positive allosteric modulators of GABAA receptors. We also consider their roles as endogenous “stress” modulators and possible additional mechanisms contributing to their therapeutic effects. We argue that further understanding of the molecular, cellular, network and psychiatric effects of neurosteroids offers the hope of further advances in the treatment of mood and anxiety disorders.
KW - Allopregnanolone
KW - Brexanolone
KW - SGE-217
KW - Steroid enantiomers
KW - Tonic inhibition
UR - http://www.scopus.com/inward/record.url?scp=85072911346&partnerID=8YFLogxK
U2 - 10.1016/j.ynstr.2019.100196
DO - 10.1016/j.ynstr.2019.100196
M3 - Article
C2 - 31649968
AN - SCOPUS:85072911346
SN - 2352-2895
VL - 11
JO - Neurobiology of Stress
JF - Neurobiology of Stress
M1 - 100196
ER -