GABA Receptor Antagonist

Bicuculline ((+)-Bicuculline) is A competing neurotransmitter GABA_A receptor antagonist (IC₅₀=2 μM). Bicuculline also blocks Ca²⁺ activating potassium (SK) channels and subsequently blocks slow post-hyperpolarization (slow AHP). Bicuculline has anticonvulsant activity. Bicuculline can be used to induce seizures in mice.

Gabazine is a selective and competitive antagonist of GABA_A receptor, with an IC₅₀ of ~0.2 μM for GABA receptor.

Furosemide is a potent and orally active inhibitor of Na⁺/K⁺/2Cl^- (NKCC) cotransporter, NKCC1 and NKCC2. Furosemide is also a GABA_A receptors antagonist and displays 100-fold selectivity for α6-containing receptors than α1-containing receptors. Furosemide acts as a loop diuretic and used for the study of congestive heart failure, hypertension and edema.

tert-Butyl 3,9-diazaspiroundecane-3-carboxylate is a 3,9-diazaspiroundecane-based building block and precursor for synthesizing γ-aminobutyric acid type A (GABA_A) receptor antagonists.

Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) is a neurosteroid and the main secretion product of the adrenal gland. Dehydroepiandrosterone sulfate has both non-competitive antagonist activity of GABA_A receptor and agonist activity of σ₁ receptor. Dehydroepiandrosterone sulfate can partially penetrate the blood-brain barrier, inhibit GABA_A receptor-mediated chloride influx, enhance NMDA receptor activity through σ₁ receptors, exert anti-inflammatory, anti-glucocorticoid and antidepressant effects, and increase convulsive sensitivity. Dehydroepiandrosterone sulfate participates in neuroprotection, neurite growth regulation and catecholamine secretion regulation, and can be used in the study of depression, post-traumatic stress disorder (PTSD), Alzheimer's disease, etc. Dehydroepiandrosterone sulfate may also be a biomarker for cardiovascular disease mortality, and its concentration is independently and negatively correlated with mortality.

Flumazenil is a competitive GABAA receptor antagonist, used in the treatment of benzodiazepine overdoses.

Picrotoxinin, a potent convulsant, is a chloride channel blocker. Picrotoxinin is a noncompetitive GABA_A receptor antagonist, which negatively modulates the action of GABA on GABA_A receptors. Picrotoxinin inhibits α₁β₂γ_2L GABA_A receptor with an IC₅₀ of 1.15 μM.

CGP52432 is a GABA_B receptor antagonist, with an IC₅₀ of 85 nM.

p-Hydroxybenzaldehyde is a one of the major components in vanilla aroma, with antagonistic effect on GABA_A receptor of the α₁β₂γ₂S subtype at high concentrations.

Primidone is the orally active inhibitor for TRPM3 (IC₅₀ = 0.6 μM), RIP kinase and voltage-gated sodium channel, and the antagonist for GABA receptor. Primidone can be used as the analgesic and anticonvulsant agent.

Dehydroepiandrosterone sulfate (DHEA sulfate; Prasterone sulfate) sodium salt is a neurosteroid and the main secretion product of the adrenal gland. Dehydroepiandrosterone sulfate sodium salt has both non-competitive antagonist activity of GABA_A receptor and agonist activity of σ₁ receptor. Dehydroepiandrosterone sulfate sodium salt can partially penetrate the blood-brain barrier, inhibit GABA_A receptor-mediated chloride influx, enhance NMDA receptor activity through σ₁ receptors, exert anti-inflammatory, anti-glucocorticoid and antidepressant effects, and increase convulsive sensitivity. Dehydroepiandrosterone sulfate sodium salt participates in neuroprotection, neurite growth regulation and catecholamine secretion regulation, and can be used in the study of depression, post-traumatic stress disorder (PTSD), Alzheimer's disease, etc. Dehydroepiandrosterone sulfate sodium salt may also be a biomarker for cardiovascular disease mortality, and its concentration is independently and negatively correlated with mortality.

(-)-Securinine is plant-derived alkaloid and also a GABA_A receptor antagonist.

Saclofen is an orally active and a competitive GABA_B receptor antagonist with an IC₅₀ of 7.8 μM. Saclofen has weak antagonistic effects on GABA_B1b and GABA_B2 heterodimeric recombinant receptors. Saclofen inhibits the binding of Baclofen (HY-B0007) to rat cerebellar membranes and blocks Baclofen-induced circadian phase shifts, and exhibits anti-inflammatory and analgesic effects in rats.

CGP55845 hydrochloride is a potent and selective GABAB receptor antagonist with an IC₅₀ of 6 nM. CGP55845 hydrochloride can be used for neurological research.

THIP (Gaboxadol) is a selective extrasynaptic GABAA receptors (eGABARs) agonist (with blood-brain barrier permeability), shows an EC₅₀ value of 13 μM for δ-GABAAR. THIP induces strong tense GABAA-mediated currents in layer 2/3 neurons, but shows on effect on miniature IPSCs. THIP can be used in studies of sleep disorders.

CGP 35348 is a selective, brain penetrant, centrally active GABAB receptor antagonist with an EC₅₀ of 34 μM. CGP 35348 shows affinity for the GABAB receptor only. CGP 35348 has a potential to improve neuromuscular coordination and spatial learning in albino mouse following neonatal brain damage.

L-Allylglycine (L-2-Allylglycine) is an amino acid derivative. L-Allylglycine is an inhibitor for glutamate decarboxylase (GAD) that reduces the GABA biosynthesis in the brain. L-Allylglycine exhibits convulsant activity.

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.

Fipronil is a broad-spectrum insecticide effective against Lepidoptera species as well as thrips, locusts, ants, cockroaches, fleas and ticks. Fipronil selectively inhibits GABA receptor with IC₅₀s of 30 nM and 1600 nM for cockroach and rat GABA receptors, respectively. Glutamate-gated chloride channels (GluCls), which are present in cockroaches but not in mammals, are sensitive to the blocking effect of Fipronil. Fipronil also induces apoptosis in HepG2 cells and promotes the expression of CYP1A1 and CYP3A4 mRNA in human hepatocytes.

Broflanilide is a potential insecticide and metabolized to Desmethyl-Broflanilide, which is a potent antagonist at the insect resistant-to-dieldrin (RDL) GABA Receptor, and inhibits S. litura RDL GABAR, with an IC₅₀ value of 1.3 nM.