gabaa receptor

GABAA receptor agent 1 has strong anticonvulsant activity and is a high affinity ligand of GABAA receptor.

GABAA receptor modulator-3 (compound 3b) is a positive allosteric modulator (PAM). It inhibits the peak current and steady-state current of α1β3γ2 GABAAR with IC50 values of 671 μM and 64 μM, respectively.

GABAA receptor modulator-4 (Compound 4) acts as a negative allosteric modulator of the GABAA receptor. It inhibits the peak and steady-state currents mediated by the α1β3γ2 GABAA receptors, with an IC50 of 10 μM for both.

α5-GABAA receptor modulator 1 (Compound A-4) is a selective silent allosteric modulator (SAM) targeting the α5 subunit of GABAA receptors, useful for research into central nervous system (CNS) disorders.

GABAA receptor modulator-7 (compound 1m), a spirobarbiturate, acts as a modulator of the GABAA receptor. It can reverse the effects of anesthetics without interfering with GABA-induced desensitization and is applicable in the research of antiepileptic and anxiolytic drugs.

GABAA receptor modulator-8 (10c) is a selective positive modulator of the GABAA receptor that can cross the blood-brain barrier and exhibits 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).

GABAA receptor agent 4 (compound 1e) is a potent antagonist of γ-GABAAR, exhibiting a Ki of 0.18 µM, and demonstrates immunomodulatory potential by effectively rescuing the inhibition of T cell proliferation [1].

GABAA receptor agent 6 (compound 2027) is a potent γ-GABAAR antagonist with low cellular membrane permeability (Ki = 0.56 μM) [1].

GABAA receptor agent 8 (compound 5e) is a potent positive modulator of the GABAA receptor, exhibiting anticonvulsant activity in both in vitro and in vivo studies, with low neurotoxicity, indicating its potential in epilepsy research [1].

GABAA receptor agonist 1 (compound 3e) is a potent agonist that binds to the GABA binding site of the GABAA receptor, producing GABAergic effects and exhibiting anti-depression activities in classical mouse models of FST and TST, indicating its potential in depression research [1].

GABAA receptor agent 7 (compound 5c) is a potent positive modulator of the GABAA receptor with anticonvulsant activity in vitro and in vivo, and low neurotoxicity, making it suitable for epilepsy research [1].

GABAA receptor agonist 2 (compound 4c) is a highly potent compound that exhibits anti-depressive properties in classical mouse models of depression, such as the FST and TST. By binding to the GABA binding site on the GABAA receptor, it produces GABAergic effects. Notably, compound 4c holds promise for depression research [1].

GABAA receptor agent 2 TFA is a potent, high-affinity GABAA receptor antagonist with an IC50 of 24 nM [human α1β2γ2GABAA-expressing tsA201 cells] and a Ki of 28 nM [rat GABAA receptor]. GABAA receptor agent 2 TFA has no effect on four human GABA transport proteins [hGAT-1, hBGT-1, hGAT-2, and hGAT-3].

GABAA receptor modulator-2 (Compound 20) is a selective, orally active α5-GABAAR negative conformation modulator (Ki: 4.1 nM) that exhibits high metabolic stability and a good central nervous system safety profile.

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.

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.

CP-409092 is a partial GABAA receptor agonist. It has anti-anxiety activity.

FG 7142 (LSU-65) also modulates GABA-induced chloride flux at GABAA receptors expressing the α1 subunit (EC50= 137 nM). FG 7142 can increase tyrosine hydroxylation and cause upregulation of β-adrenoceptors in mouse cerebral cortex. FG 7142 , a non-selectively benzodiazepine inverse agonist, has high affinity for the α1 subunit-containing GABAA receptor (Ki=91 nM).

Valnoctamide (Valmethamide) has antiepileptic and anticonvulsant activity and can be used in the study of neurological disorders.

Songorine (Napellonine) shows favorable anti-tumor activity in preliminary pharmacological verification trials including cell proliferation and molecular docking assays.

Urethane (Ethyl carbamate; Ethylurethane) is a byproduct formed during the fermentation process of various foods. As an ethyl ester of carbamic acid, it has the ability to inhibit the growth of bacteria, sea urchin eggs, protozoa, and plant tissues, and is commonly used for establishing lung cancer models.

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.

LAU159 is a functionally selective positive α1β3 GABA(A) receptor modulator (EC50: 2.2 μM).