GABA Receptor Modulator

Isovaleramide (3-Methylbutanamide) is an orally active anticonvulsant. Isovaleramide inhibits alcohol dehydrogenase (ADH) activity and regulates GABAergic system. Isovaleramide reduces acute kidney injury. Isovaleramide has antiepileptic, anxiolytic, sedative and hypnotic effects[1].

7-Keto-DHEA binds to GABA Receptor, and reduces the ethanol intake in rats. 7-Keto-DHEA exhibits potential in investigation of alcohol dependence disorders.

CGP13501 is a positive allosteric modulator of GABAB receptor. CGP13501 is a structural analogue of propofol.

Lorediplon is a novel non-benzodiazepine drug acting as a GABAA receptor modulator, differentially active at the alpha1-subunit, associated with promoting sleep.

CGP7930 (3-(3’,5’-Di-tert-butyl-4’-hydroxy) phenyl-2, 2-dimethylpropanol) is a positive metabotropic GABAB receptor allosteric modulator. CGP7930 enhances the inhibitory effect of l-baclofen on the oscillatory activity of cultured cortical neurons.

ADX71441 is an orally active, blood-brain barrier penetrant positive allosteric modulator of GABA_B receptor. ADX71441 potentiates the activity of endogenous GABA at GABA_B receptor, with an EC₅₀ of 96 nM. ADX71441 functionally inhibits adenosine transporters and 5-HT_2B receptor. ADX71441 produces anxiolytic-like, analgesic, muscle relaxant, hypothermic and overactive bladder inhibitory effects, reduces acute locomotor activity levels, decreases voluntary intake of alcohol and saccharin, attenuates stress-induced neuronal activation, and exhibits anti-hyperalgesic activity.

Ocinaplon (DOV 273547) is an orally active positive allosteric modulator of GABA_A receptor, with an EC₅₀ ranging from 3.07 μM (α1β2γ2 subtype) to 10.03 μM (α1β2γ3 subtype). Ocinaplon enhances GABA-stimulated chloride currents across multiple GABA_A receptor subtypes, with varying potency between different subtypes. Ocinaplon exerts anxiolytic and anticonvulsant effects, and causes motor impairment at high doses. Ocinaplon can be used for research on generalized anxiety disorder.

AZD6280 is an orally active, blood-brain barrier-permeable GABA_A receptor modulator, with K_i values of 21 nM, 31 nM and 1680 nM against human receptors containing α2, α3 and α5 subtypes, respectively, and subtype-specific K_i values of < 30 nM for α2 and α3 subtypes. AZD6280 selectively potentiates GABA_A receptors containing α2/α3 subtypes with higher potency than α1/α5 subtypes, exerts no modulatory effect on receptors containing α1 subtypes, and regulates the tuberoinfundibular dopaminergic pathway. AZD6280 decreases peak saccadic velocity, increases serum and plasma prolactin levels, rescues dendritic abnormalities of cortical neurons induced by DISC1 knockdown. AZD6280 can be used in studies related to anxiety disorders.

NS11394 is an orally active and unique subtype-selective GABA_A positive allosteric receptor (PAM), with a K_i of ~0.5 nM. NS11394 shows a selectivity profile in the order of GABA_A-5 > α3 > α2 > α1-containing receptors. NS11394 has anxiolytic and anti-inflammatory properties.

ONO-8590580 is a GABA_A α5 negative allosteric modulator.

MIDD0301 (GL-II-93) is an orally available, active γ-aminobutyric acid type A receptor (GABA_AR) inhibitor and anti-asthmatic agent. MIDD0301 exhibits biological and immunotoxicological safety in mice and does not affect the number of circulating lymphocytes, monocytes, and granulocytes. MIDD0301 has no significant adverse immune response at repeated doses, which is better than Prednisone (HY-B0214). MIDD0301 relaxes histamine-contracted guinea pig and human airway smooth muscle and is used in the study of bronchoconstrictive diseases.

Abecarnil (ZK 112119) is a ligand or a partial agonist for benzodiazepine (BZ) receptor. Abecarnil possesses anxiolytic and anticonvulsant properties. Abecarnil can act as a positive allosteric modulator of GABA_A receptor. Abecarnil inhibits the binding of the BZ [3H]lormetazepam to rat cerebral cortex membranes, with an IC₅₀ of 0.82 nM. Abecarnil can be used for epilepsy research.

Spinosyn J is a non-competitive insect nicotinic acetylcholine receptor (nAChR) and γ-aminobutyric acid (GABA) receptor modulator with insecticidal activity. Spinosyn J is promising for research of agricultural pests.

(S)-Padsevonil is the S-enantiomer of Padsevonil (HY-109009).Padsevonil (UCB0942) is a potent antiepileptic agent that selectively acts on presynaptic and postsynaptic targets. Padsevonil binds to synaptic vesicular protein 2 (SV2) with high affinity. Padsevonil is also a positive allosteric modulator and partial agonist of GABA_AR, with high potency against α1 and α5 receptors. Padsevonil has antiepileptic effects in a variety of rodent models.

Etiocholanolone-d₅ is the deuterium labeled Etiocholanolone. Etiocholanolone (5β-Androsterone) is the excreted metabolite of testosterone and has anticonvulsant activity. Etiocholanolone is a less potent?neurosteroid positive allosteric modulator?(PAM) of the GABAA?receptor than its?enantiomer form.

Delta3,5-cholestadien-7-one is an oxysterol and a negative allosteric modulator of GABAA receptors. Delta3,5-cholestadien-7-one reduces GABA-induced currents in HEK cells expressing α1β1γ2 or α4β3γ2 subunit-containing GABAA receptors with IC₅₀ values of 1.5 and 1 µM, respectively. Delta3,5-cholestadien-7-one reduces GABA-induced depolarization of peptidergic and non-peptidergic nociceptors, C-LTMRs, and cold thermosensors in isolated mouse dorsal root ganglion (DRG) neurons.

Creatinine-¹⁵N (NSC13123-¹⁵N) is the ¹⁵N-labeled Creatinine (HY-B0504). Creatinine (NSC13123) is an orally active, blood-brain barrier-permeable modulator of GABAA and NMDA receptors, with activities of antioxidation and metabolic regulation. Creatinine is generated via non-enzymatic conversion of creatine and phosphocreatine in muscle. Creatinine serum levels correlate with muscle mass, glomerular filtration rate, and extrarenal clearance, serving as an evaluation biomarker for renal function, muscle mass, and clinical outcomes, and used for perioperative renal risk assessment. In addition, Creatinine can induce specific Cryptococcus species to produce creatinine deiminase and act as their nitrogen source, while it can be secreted via renal tubules. Creatinine is widely used in research related to various diseases such as neurodegenerative diseases, psychiatric disorders, acute kidney injury, chronic kidney disease, and renal failure.

SB-205384 is a GABAA receptor modulator. The primary effect of SB-205384 on GABAA-activated currents is a prolonged response decay half-life upon removal of the agonist.

GABAA receptor modulator-14 is an orally active, blood-brain barrier permeable selective positive allosteric modulator (PAM) of extrasynaptic δ-containing GABA_A receptors (α4β3δ subtype) with an EC₅₀ of 0.8 μM. GABAA receptor modulator-14 selectively enhances tonic neuronal inhibition by potentiating GABA-evoked currents mediated by extrasynaptic δ-GABA_ARs, produces rapid sustained antidepressant effects, elevates slow-wave NREM sleep and shows no addiction liability in mice. GABAA receptor modulator-14 can be applied to major depressive disorder (MDD) and comorbid insomnia research.

Necopidem (Compound 6) is a GABA A receptor modulator. Necopidem can be used in research on neurological disorders such as anxiety.