PF-06372865 is a novel potent, α2/3 functionally selective GABAA receptor positive allosteric modulator; exhibits functional selectivity for receptors containing α2/3/5 subunits, with significant positive allosteric modulation (90-140%) but negligible activity (<20%) at GABAA receptors containing α1 subunits; demonstrates a robust increase in saccadic peak velocity, increases in beta frequency qEEG and a slight saturating increase in body sway in clinical trials. Epilepsy Phase 1 Clinical
SX-3228 is a selective benzodiazepine1 (BZ1) receptor agonist with an IC50 of 17 nM.
Emamectin Benzoate (MK-244) works as a chloride channel activator by binding gamma aminobutyric acid (GABA) receptor and glutamate-gated chloride channels disrupting nerve signals within arthropods.
Oxiracetam is a cyclic derivative of γ-aminobutyric acid (GABA) which has been commonly used as nootropic drug to treat cognitive impairments.
Lesogaberan (AZD-3355) is a potent and selective GABAB receptor agonist with an EC50 of 8.6 nM for human recombinant GABAB receptors. Binding affinity (Kis) of 5.1 nM and 1.4 μM for rat brain GABAB and GABAA receptors, respectively[1].
Rilmazafone is a benzodiazepine (omega) ligand with sedative and hypnotic effects[1].
Piperidine-4-sulfonic acid is a potent GABA agonist with an IC50 of 0.034 μM for the inhibition of the binding of H-GABA[1].
(S)-Cipepofol is the inactive isomer of Cipepofol (HY-116152).Cipepofol (HSK3486) is a sleep-promoting active molecule and a gamma-aminobutyric acid (GABA) receptor enhancer[1].
mGAT3/4-IN-2 (compound 27b) is a potent mGAT3/mGAT4 inhibitor, with pIC50 values of 5.44 and 5.25, respectively[1].
(+)-Borneol (d-Borneol) is a natural bicyclic monoterpene used for analgesia and anesthesia in traditional Chinese medicine; enhances GABA receptor activity with an EC50 of 248 μM.
GABAA receptor agent 6 (compound 2027) is a potent γ-GABAAR antagonist with an Ki of 0.56 µM. GABAA receptor agent 6 shows γ-GABAAR antagonist activity with low cellular membrane permeability[1].
Anxiolytic/nonsedative agent-1 (compound 2b) is a potent and selective GABAA agonist. Anxiolytic/nonsedative agent-1 shows appreciable affinity for the BzR in bovine brain membranes with Kis of 14, 121, 239 nM for α1β2γ2, α2β2γ2, α5β3γ2, respectively. Anxiolytic/nonsedative agent-1 shows α2 selective efficacy in vitro and anxioselective effects in vivo[1].
Bicuculline ((+)-Bicuculline; d-Bicuculline) methochloride is a selective GABAA receptor antagonist with an IC50 value of 3 μM. Bicuculline methochloride induces clonic tonic convulsions in mammals and can also be used to block Ca2+ activated potassium channels. Bicuculline methochloride can be used in studies of epilepsy and other related psychiatric disorders[1][2].
Alogabat (example 8) is a GABAA α5 receptor positive allosteric modulators (PAMs) (extracted from patent WO2018104419A1)[1].
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
CP-409092 is a GABA(A) partial agonist, used for the treatment of anxiety.
Topiramate (McN 4853) lithium is a broad-spectrum antiepileptic agent. Topiramate lithium is a GluR5 receptor antagonist. Topiramate produces its antiepileptic effects through enhancement of GABAergic activity, inhibition of kainate/AMPA receptors, inhibition of voltage-sensitive sodium and calcium channels, increases in potassium conductance, and inhibition of carbonic anhydrase[1][2][3].
(-)-Bicuculline methobromide (l-Bicuculline methobromide) is a potent GABAA receptor antagonist. (-)-Bicuculline methobromide blocks afterhyperpolarizations (AHPs) mediated by Ca2+-activated K+ channels in various types of neurons[1].
(2S)-6-Prenylnaringenin is the most efficient compound in forebrain. (2S)-6-Prenylnaringenin acts as a GABAA positive allosteric modulator at α+β- binding interface[1].
FG8119 is a novel benzodiazepine agonist extracted from patent US 4745112 A.
6-methylflavone is an activator of α1β2γ2L and α1β2 GABAA receptors.
Etiocholanolone (5β-Androsterone) is the excreted metabolite of testosterone and has anticonvulsant activity[1]. Etiocholanolone is a less potent neurosteroid positive allosteric modulator (PAM) of the GABAA receptor than its enantiomer form[2].
3-Methylglutaconic acid is the major metabolites accumulating in 3-Methylglutaconic aciduria (MGTA). 3-Methylglutaconic acid can induce lipid oxidative damage and protein oxidative. 3-Methylglutaconic acid decreases the non-enzymatic antioxidant defenses in cerebral cortex supernatants to elicit oxidative stress in the cerebral cortex. 3-Methylglutaconic acid can be used for brain damage disease research[1].
THIP (Gaboxadol) is a selective δ-aminobutyric acid type A receptor (δ-GABAAR) agonist, functionally selective GABAAR ligand, exhibits agonism at α4β1δ, α4β3δ and weak antagonism at αβγ and α4β2δ GABAARs[1].
Cipepofol (HSK3486), a sedative-hypnotic agent, is a gamma-aminobutyric acid (GABA) receptor potentiator[1].
p-Hydroxybenzaldehyde-d5 is the deuterium labeled p-Hydroxybenzaldehyde[1]. p-Hydroxybenzaldehyde is a one of the major components in vanilla aroma, with antagonistic effect on GABAA receptor of the α1β2γ2S subtype at high concentrations[2].
DAA1106 is a potent and selective ligand for peripheral benzodiazepine receptor (PBR), as a potent and selective agonist at the peripheral benzodiazepine receptor.Target:PBRin vitro: DAA1106 binding to PBR was significantly increased in widespread areas in MCI subjects when compared to healthy controls.[1] DAA-1106 is a drug which acts as a potent and selective agonist at the peripheral benzodiazepine receptor, also known as the mitochondrial 18 kDa translocator protein or TSPO, but with no affinity at the GABAA receptor. [2]in vivo: DAA-1106 has anxiolytic effects in animal studies. DAA-1106 has a sub-nanomolar binding affinity (Ki) of 0.28nM, and has been used extensively in its 3H or 11C radiolabelled form to map TSPO in the body and brain, which has proved especially helpful in monitoring the progress of neurodegenerative diseases such as Alzheimer's disease. [2]
Ginsenoside Rc, one of major Ginsenosides from Panax ginseng, enhances GABA receptorA (GABAA)-mediated ion channel currents (IGABA). Ginsenoside Rc inhibits the expression of TNF-α and IL-1β.
TPA 023 is a GABAA α2/α3 subtype-selective agonist, with Ki of 0.19-0.41 nM.
DL-Pyroglutamic acid (CAE) as an inactivator of hepatitis B surface, inactivates vaccinia virus, herpes simplex virus, and influenza virus except poliovirus. DL-Pyroglutamic acid is also a possible inhibitor of GABA transaminase, increases GABA amount with antiepileptic action[1][2].