Tetrahydrodeoxycorticosterone, an neurosteroid, is a potent positive allosteric modulator (PAM) of GABAA receptor. Tetrahydrodeoxycorticosterone has potent neuroinhibitory properties[1][2].
The endogenous neurosteroid Tetrahydrodeoxycorticosterone (THDOC) at physiological concentrations selectively enhances tonic currents mediated by αβδ receptors[1].In hippocampus, 10 nM Tetrahydrodeoxycorticosterone reduces neuronal excitability by augmenting tonic αβδ receptor currents. In thalamocortical neurons, although 100 nM Tetrahydrodeoxycorticosterone enhances tonic currents, 10 nM Tetrahydrodeoxycorticosterone does not[1].
Concentrations of Tetrahydrodeoxycorticosterone (THDOC) in brain tissue from mice with hepatic encephalopathy (HE) resulting from toxic liver injury are sufficient to induce sedation in animals of the same species[2].
[1]. Hua-Jun Feng, et al. Comparison of αβδ and αβγ GABA A receptors: Allosteric modulation and identification of subunit arrangement by site-selective general anesthetics. Pharmacol Res. 2018 Jul;133:289-300.
[2]. Roger F Butterworth. Neurosteroids in hepatic encephalopathy: Novel insights and new therapeutic opportunities. J Steroid Biochem Mol Biol. 2016 Jun;160:94-7.