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Non-Feminizing Estrogens Do Not Exhibit Antidepressant-like Activity.

Katalin Prokai-Tatrai1, Vien Nguyen1, Laszlo Prokai1

  • 1Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA.

Journal of Pharmaceutics and Drug Research
|February 28, 2017
PubMed
Summary

Non-feminizing estrogens show increased antioxidant power but fail as menopause treatments due to poor drug-like properties. Genomic mechanisms are essential for treating depression linked to estrogen deprivation.

Keywords:
AntidepressantDrug-likenessEstrogensNon-feminizingPorsolt swim test

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Area of Science:

  • Endocrinology
  • Neuroscience
  • Pharmacology

Background:

  • Menopausal symptoms and associated neurological/psychiatric conditions represent unmet medical needs.
  • Estrogen deprivation impacts brain function, particularly mood regulation.
  • Non-feminizing estrogens are explored as potential therapeutic agents.

Purpose of the Study:

  • To evaluate non-feminizing estrogens as lead compounds for treating menopausal symptoms.
  • To assess their efficacy in addressing neurological and psychiatric conditions linked to estrogen deprivation.
  • To investigate the mechanisms underlying their effects on mood.

Main Methods:

  • Exploratory study involving prototype structure synthesis and lipophilicity assessment.
  • Evaluation of pharmaceutical properties and drug-likeness.
  • Assessment in an animal model of estrogen deprivation to study mood effects.

Main Results:

  • Increased lipophilicity enhanced antioxidant potency of prototype non-feminizing estrogens.
  • Significant shortcomings were identified in pharmaceutically important properties and drug-likeness.
  • Genomic mechanisms were confirmed as necessary for alleviating menopause-associated depression in an animal model.

Conclusions:

  • Non-feminizing estrogens possess enhanced antioxidant capacity but are unsuitable for therapeutic development due to poor drug-like qualities.
  • These compounds cannot fulfill the premise of treating neurological and psychiatric conditions associated with estrogen deprivation.
  • Genomic pathways are critical for addressing mood disorders linked to the loss of estrogen.