Anticonvulsant profile of the progesterone metabolite 5 alpha-pregnan-3 alpha-ol-20-one

Eur J Pharmacol. 1989 Jul 18;166(2):325-9. doi: 10.1016/0014-2999(89)90077-0.

Abstract

5 alpha-Pregnan-3 alpha-ol-20-one (3 alpha-OH-DHP) is a naturally occurring metabolite of progesterone that can modulate brain excitability through a specific steroid recognition site on the GABA/benzodiazepine receptor-chloride ionophore complex. The anticonvulsant properties of 3 alpha-OH-DHP were determined using standardized anticonvulsant screening tests in mice. This steroid was found to be effective against metrazol-, (+)-bicuculline- and picrotoxin-induced seizures. The steroid has maximum potency against (+)-bicuculline-induced convulsions and no activity against maximal electroshock and strychnine-induced seizures. These findings support the hypothesis that therapeutically useful anticonvulsant steroids active at the putative steroid recognition site associated with the GABA/benzodiazepine receptor-chloride ionophore complex can be identified.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Hypnotics and Sedatives
  • Lethal Dose 50
  • Male
  • Mice
  • Pregnanes / pharmacology*
  • Pregnanolone / pharmacology*
  • Pregnanolone / toxicity
  • Seizures / chemically induced
  • Seizures / prevention & control

Substances

  • Anticonvulsants
  • Hypnotics and Sedatives
  • Pregnanes
  • Pregnanolone