Development and screening of water-soluble analogues of progesterone and allopregnanolone in models of brain injury

J Med Chem. 2009 Oct 8;52(19):6012-23. doi: 10.1021/jm900712n.


Preclinical and clinical research findings have revealed that the hormone progesterone, when acutely administered, can dramatically reduce cerebral edema, inflammation, tissue necrosis, and programmed cell death following traumatic brain injury (TBI). The poor aqueous solubility of progesterone, however, limits its potential use as a therapeutic. Several chemically novel analogues of progesterone and its natural metabolite allopregnanolone have been synthesized and screened using both in vitro and whole animal models of TBI. The new derivatives demonstrated greatly improved solubility and select compounds have shown equivalent effectiveness to progesterone in reducing cerebral edema after TBI.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Edema / drug therapy
  • Brain Injuries / drug therapy*
  • Drug Evaluation, Preclinical
  • Female
  • Ketones
  • Male
  • Models, Animal
  • Oximes
  • Pregnanolone / analogs & derivatives*
  • Pregnanolone / chemistry
  • Pregnanolone / therapeutic use
  • Progesterone / analogs & derivatives*
  • Progesterone / chemistry
  • Progesterone / therapeutic use
  • Rats
  • Solubility
  • Structure-Activity Relationship


  • Ketones
  • Oximes
  • Progesterone
  • Pregnanolone