Certain endogenous steroids are modulators of GABAA receptors. Tetrahydroprogesterone (THP, 5 alpha-pregnan-3 alpha-ol-20-one) and tetrahydrodeoxy-corticosterone (THDOC, 5 alpha-pregnane-3 alpha, 21-diol-20-one) behave as allosteric agonists of GABAA receptors whereas pregnenolone sulphate acts as an antagonist. THP and THDOC modulate ligand binding to GABAA receptors like barbiturates; they potentiate binding of the GABAA receptor agonist muscimol and the benzodiazepine flunitrazepam and they allosterically inhibit binding of the convulsant t-butylbicyclophosphorothionate.
The Journal of Pharmacology and Experimental Therapeutics
GABA(A) receptors have been implicated in mediating several acute effects of ethanol including anxiolysis, ataxia, sedation/hypnosis, and anticonvulsant activity. Ethanol sensitivity of neurons has been associated with expression of alpha1 subunit-containing receptors. The objective of this study was to determine the contribution of alpha1 subunit containing receptors to ethanol responses in comparison to neurosteroids and other anesthetics using GABA(A) receptor alpha1 subunit knockout mice.