GABAA receptor modulator-10 is an orally active and potent positive allosteric modulator (PAM) of the α1β2γ2GABAA receptor, exhibiting good blood-brain barrier permeability. It enhances the function of the α1β2γ2 GABAA receptor and increases GABA-induced currents. In mouse models of epilepsy induced by Pentetrazol (PTZ) and Kainic Acid (KA), GABAA receptor modulator-10 demonstrates strong antiepileptic efficacy. This compound shows potential for epilepsy research.

GABAA receptor modulator-10 (Compound 10) (10 μM) enhances the function of α1β2γ2 GABA_A receptors in HEK293T cells overexpressing α1β2γ2 GABA_A receptors through an MQAE-based fluorescence assay. At concentrations ranging from 0.1 to 100 μM, GABAA receptor modulator-10 increases GABA-induced currents in these cells in a concentration-dependent manner, as determined by patch-clamp technique (EC50 = 1.99 μM, Emax = 80.1%).

GABAA receptor modulator-10 (Compound 10) (10 μM, pre-exposure 3 hours before PTZ treatment) reduced the total distance moved in AB strain zebrafish 6 days post-fertilization. Additionally, GABAA receptor modulator-10 (0.3-30 mg/kg, administered orally 1 hour before PTZ injection) increased the latency of stage I and stage III seizures, decreased the duration of stage III seizures, and prevented stage V seizures in a PTZ-induced mouse seizure model. Furthermore, GABAA receptor modulator-10 (30 mg/kg, orally administered 30 minutes prior to KA injection) mitigated seizure severity and reduced mortality in a KA-induced mouse temporal lobe epilepsy model.