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Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond.

Authors
  • Zorumski, Charles F1, 2, 3
  • Paul, Steven M1, 4, 3
  • Covey, Douglas F1, 5, 3
  • Mennerick, Steven1, 2, 3
  • 1 Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • 2 Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA.
  • 3 The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA.
  • 4 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
  • 5 Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
Type
Published Article
Journal
Neurobiology of stress
Publication Date
Nov 01, 2019
Volume
11
Pages
100196–100196
Identifiers
DOI: 10.1016/j.ynstr.2019.100196
PMID: 31649968
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. © 2019 The Author(s).

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