Affordable Access

deepdyve-link
Publisher Website

Allopregnanolone: From molecular pathophysiology to therapeutics. A historical perspective.

Authors
  • Paul, Steven M1, 2, 3
  • Pinna, Graziano4
  • Guidotti, Alessandro4, 5
  • 1 Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
  • 2 The Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO, USA.
  • 3 Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
  • 4 The Psychiatric Institute, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
  • 5 Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of IIIinois at Chicago, USA.
Type
Published Article
Journal
Neurobiology of stress
Publication Date
May 01, 2020
Volume
12
Pages
100215–100215
Identifiers
DOI: 10.1016/j.ynstr.2020.100215
PMID: 32435665
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Allopregnanolone is synthesized in the central nervous system either de novo from cholesterol or from steroid hormone precursors like progesterone and pregnenolone. Over the past 30 years, direct and rapid, non-genomic actions of allopregnanolone and its derivatives via GABAA receptors have been demonstrated. Changes in brain levels of allopregnanolone during pregnancy and in the postpartum period, or during exposure to protracted stress appear to play a crucial role in the pathophysiology of mood disorders. The discovery that allopregnanolone at low (nanomolar) concentrations elicits marked anxiolytic, anti-stress and antidepressant effects by facilitating allosterically the action of GABA at extrasynaptic GABAA receptors has provided new perspectives for the discovery of novel drugs useful for the treatment of mood disorders. These findings have led to the seminal clinical studies that recently demonstrated that treatment with allopregnanolone (i.e., brexanolone) can dramatically and rapidly improve the symptoms of postpartum depression in many patients. © 2020 The Authors.

Report this publication

Statistics

Seen <100 times