α1β2γ2 gabaa receptor

Glabridin (KB-289522) may serve as an anti-inflammatory agent in diabetes-related vascular dysfunction, through regulating the synthesis and activity of iNOS under high-glucose levels; may possess a therapeutic effect on metabolic disorders( such as diabetes and hyperglycemia), by modulating glucose metabolism through AMPK in skeletal muscle cells. Glabridin may have potential as a chemopreventive agent against liver Y metastasis, by inhibiting the invasion of human HCC cells.

GABAA receptor agent 5 demonstrates antagonist activity across multiple GABAA receptor subtypes, and GABAA receptor agent 5 exhibits IC50 values of 0.24, 0.088, 0.068, 0.33, 0.79, 0.32, 0.079, and 0.051 μM for α1β2δ, α4β1δ, α4β2δ, α6β2δ, α1β2γ2, α2β2γ2, α3β2γ2, and α5β2γ2 receptor configurations, respectively. GABAA receptor agent 5 (compound 018) thereby provides a precise pharmacological tool for characterizing subtype-selective GABAA receptor inhibition and supports mechanistic neuropharmacology studies focused on inhibitory synaptic signaling and therapeutic antagonist development.

Etifoxine hydrochloride (HOE 36-801 hydrochloride) is an anxiolytic and anticonvulsant drug. Unlike benzodiazepines, Etifoxine hydrochloride appears to produce its anxiolytic effects by binding to β2 and β3 subunits of the GABAA receptor complex, and so is acting at a different target site to benzodiazepines, although the physiological effect that is produced is similar to that of benzodiazepines.

Anticonvulsant agent 9 (compound 4f) is an activator of the α1β2γ2GABA_A receptor, with an EC50 value of 1.24 μM. It inhibits the inactivation of Nav1.2 channels and exhibits significant anticonvulsant activity.

GABAA receptor modulator-9 is a positive allosteric modulator of the GABAA receptor, specifically targeting the α1β2γ2 subtype and capable of crossing the blood-brain barrier. It exhibits excellent activity at α1β2γ2 (EC50: 0.9 μM in oocytes and 0.2 μM in CHO cells) and also shows activity at α1β2, α3β2γ2, and α1β3γ2 (with EC50 values of 1.3, 3.4, and 1.1 μM, respectively). GABAA receptor modulator-9 significantly inhibits seizure progression and reduces mortality in mice. It is applicable in studies of status epilepticus (SE).

TP003 is a novel non-selective GABAA receptor benzodiazepine site agonist with affinity for α1β2gam2, α2β3gam2, α3β3gam2, α5β2gam2, EC50 of 20.3, 10.6, 3.24, 5.64 nM, respectively. TP003 has antianxiety and partial anticonvulsant activity via the α2GABAA receptor.

Compound S28, also known as GABAA receptor modulator-3, regulates the (γ-aminobutyric acid)A receptor (GABAA receptor), exhibiting EC50 values of 56 nM for the α1β2γ2 subtype and 10 nM for the α4β3δ subtype. In rats, it demonstrates favorable pharmacokinetic properties and slight toxicity. The threshold dose for loss of righting reflex (LORR) in rats is 23.3 μmol/kg. Furthermore, Compound S28 shows potential to alleviate postpartum depression.