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Progesterone: does it affect response to drug?

P D Kroboth1, J W McAuley

  • 1Department of Pharmaceutical Sciences, University of Pittsburgh, School of Pharmacy, PA, USA.

Psychopharmacology Bulletin
|January 1, 1997
PubMed
Summary
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Progesterone increases sensitivity to triazolam, a benzodiazepine, by enhancing the gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex (GBRC). This finding supports in vitro data on progesterone

Area of Science:

  • Neuropharmacology
  • Endocrinology

Background:

  • The gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex (GBRC) is a key target for sedative-hypnotic drugs.
  • Progesterone and its metabolites, such as tetrahydroprogesterone (THP), are known to interact with the GBRC.

Purpose of the Study:

  • To investigate the in vitro modulation of the GBRC by THP.
  • To evaluate the in vivo effects of a single oral dose of progesterone on triazolam sensitivity in post-menopausal women.

Main Methods:

  • In vitro studies examining THP's effect on benzodiazepine binding to the GBRC.
  • A single-dose study involving 16 post-menopausal women pre-treated with oral progesterone before a triazolam challenge dose.

Main Results:

  • In vitro data showed THP enhances benzodiazepine binding to the GBRC.

Related Experiment Videos

  • Progesterone pre-treatment (300 mg oral) significantly increased triazolam sensitivity in women.
  • Triazolam's EC50 decreased by 20-32% after progesterone administration.

    • Conclusions:

    • Progesterone enhances the effects of benzodiazepines like triazolam, likely via the GBRC.
    • These findings support the neuroactive role of progesterone and its metabolites.
    • Further research is needed to explore the clinical implications for other steroids.