GABAR (Gamma-aminobutyric acid Receptor) belongs to the superfamily of ligand-gated ion channels, and is formed by an assembly of five homologous subunits. Besides, GABAR also is the major inhibitory neurotransmitter in the central nervous system. Importantly, A large number of clinically used psychoactive drugs exert their effects mainly or exclusively via interaction with GABA receptors. So, the GABA receptors inhibitor has the potent for the research of the neurological disease.

In this article, we will introduce a potent, allosteric and selective GABA receptor inhibitor, SCS.

SCS (salicylidene salicylhydrazide) is a GABA receptor inhibitor with a maximum inhibition of 56% and an IC50 value of 32 nm against α2β1γ1θ. Besides, SCS shows inhibition for α2β1γ1θ, α2β1γ1, α1β1γ2s with IC50s of 4.5, 5.3, 7.9 nM, respectively. Moreover, SCS (0.1 nM-3 μM) produces a concentration-dependent inhibition of GABA EC20 currents recorded from Ltk cells expressing α2β1γ1θ, α2β1γ1 and α1β1γ2s receptors compared with α2β3γ2s and α1β2γ2s receptors upon which SCS has no effect. In addition, Structural determinants necessary for the inhibition of GABA receptors by SCS are located within the region arginine 238 and glycine 335 of the β1 subunit. T255 and I308 of the β1 subunit are required for inhibition by SCS.

SCS (500-1000 mg/kg, i.p. or 800-1000 mg/kg, oral) produces abdominal constrictions in mice. Moreover, SCS (10-75 mg/kg; i.p.; once) shows antinociceptive activity against tonic, phasic and Capsaicin (HY-10448) nociception in mice. Meanwhile, SCS (10-75 mg/kg; i.p.; once) shows anti-inflammatory activity in mice. Additionally, SCS (50 and 75 mg/kg; i.p.; once) shows antinociceptive activity against neuropathic nociception.

All in all, SCS is a potent, allosteric and selective GABA receptor inhibitor and shows anti-inflammatory, antinociceptive activity.


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[2] Rukh L, et al. Eur J Pharmacol. 2020 Dec 5;888:173481.