Modulation of the GABA receptor complex by a steroid anaesthetic

Brain Res. 1984 Dec 10;323(2):287-92. doi: 10.1016/0006-8993(84)90299-3.


The interactions of a steroid anaesthetic, alphaxalone, with the GABA receptor-ionophore complex were investigated by two different experimental approaches. In the rat cuneate nucleus slice, alphaxalone (0.1-10 microM) potentiated depolarizing responses to superfused GABA and muscimol, but not those to glycine. The potentiating effect of alphaxalone was unaltered by the benzodiazepine antagonist Ro 15-1788. Alphaxalone (0.1-30 microM) also enhanced [3H]muscimol binding to rat brain membranes in the presence of Cl-ions; the enhancing effect on [3H]muscimol binding was abolished by Triton X-100. Analysis of binding curves for [3H]muscimol indicated that the steroid anaesthetic increases the affinity for [3H]muscimol of low affinity binding sites; this property is shared by pentobarbitone. The physiologically inactive beta-hydroxy isomer of the steroid was without activity in either of the experimental situations at 30 microM. It is suggested that alphaxalone and pentobarbitone share a common mode of action on the GABA system, which may be relevant to the mechanisms by which these drugs produce anaesthesia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics / pharmacology*
  • Animals
  • In Vitro Techniques
  • Male
  • Medulla Oblongata / drug effects*
  • Muscimol / metabolism
  • Pentobarbital / pharmacology
  • Pregnanediones / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Receptors, Muscarinic / drug effects


  • Anesthetics
  • Pregnanediones
  • Receptors, Adrenergic, alpha
  • Receptors, GABA-A
  • Receptors, Muscarinic
  • Muscimol
  • alphaxalone
  • Pentobarbital