A putative receptor for neurosteroids on the GABAA receptor complex: the pharmacological properties and therapeutic potential of epalons

Crit Rev Neurobiol. 1995;9(2-3):207-27.

Abstract

A critical mass of evidence now supports the existence of a novel class of neuroactive steroids. These steroids are devoid of any known steroid hormone activity and have high specificity for the gamma-aminobutyric acidA receptor complex (GRC), which is a ligand-gated chloride channel that mediates the inhibitory action of the neurotransmitter gamma-aminobutyric acid (GABA). The action of these steroids at the GRC is to allosterically potentiate the effect of GABA on chloride channel conductance through a unique site on the GRC. These neuroactive steroids have been termed the epalons, a shortened form of epiallopregnanolone, an endogenous metabolite of progesterone with potent actions at the GRC. Putative epalon receptors may be unique sites on the GRC that mediate the effects of epalons on GABA-gated channel function. The pharmacological profile of the epalons is consistent with those of other positive modulators of GABA action (e.g., the clinically useful benzodiazepines (BZs) and barbiturates). These neuroactive steroids have anxiolytic, anticonvulsant, and sedative-hypnotic properties. Based upon some of the unique characteristics of the epalons relative to barbiturates and the BZs, it is plausible that the epalons can be developed into a novel class of therapeutic agents for the treatment of anxiety, epilepsy, and insomnia.

Publication types

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

MeSH terms

  • Brain / metabolism*
  • GABA-A Receptor Agonists
  • Humans
  • Pregnanolone / pharmacology
  • Pregnanolone / therapeutic use
  • Receptors, GABA-A / metabolism*
  • Receptors, GABA-A / ultrastructure
  • Receptors, Steroid / agonists
  • Receptors, Steroid / metabolism*
  • Steroids / metabolism*

Substances

  • GABA-A Receptor Agonists
  • Receptors, GABA-A
  • Receptors, Steroid
  • Steroids
  • Pregnanolone