Primidone is an anticonvulsant of the pyrimidinedione class.Target: GABA ReceptorPrimidone is an anticonvulsant of the pyrimidinedione class, the active metabolites of which, phenobarbital (minor) and phenylethylmalonamide (PEMA) (major), are also anticonvulsants. It is believed to work via interactions with voltage-gated sodium channels which inhibit high-frequency repetitive firing of action potentials [1]. The effect of primidone in essential tremor is not mediated by PEMA.[76] The major metabolite, phenobarbital, is also a potent anticonvulsant in its own right and likely contributes to primidone's effects in many forms of epilepsy [2]. Primidone and the other enzyme-inducing anticonvulsants can cut the half-life of antipyrine roughly in half (6.2 ± 1.9 h vs. 11.2 ± 4.2 h), and increases the clearance rate by almost 70%. Phenobarbital reduces the half-life to 4.8 ± 1.3 and increases the clearance by almost 109% [3].
SCH 50911 hydrochloride, (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid, a selective, orally-active and competitive γ-Aminobutyric acid B GABA(B) receptor antagonist, binds to GABA(B) receptor with IC50 of 1.1 μM. SCH 50911 hydrochloride antagonizes GABA(B) autoreceptors, increasing the electrically-stimulated 3H overflow with an IC50 of 3 μM.
CGP13501 is a positive allosteric modulator of GABAB receptor. CGP13501 is a structural analogue of propofol[1].
RWJ-51204 is a partial agonist of GABA(A) receptor, with Ki of 0.2-2 nM to the benzodiazepine site on GABA(A) receptors.
Cirsimaritin binds weakly to the benzodiazepine site on GABAA receptors, with antidepressant, anxiolytic and antinociceptive activities.
MK0343 (MRK-409) is an orally bioavailable GABAA receptor subtype-selective partial agonist. MK0343 is a non-sedating anxiolytic[1].
Etazolate hydrochloride (SQ 20009) is an orally active, selective inhibitor of type 4 phosphodiesterase (PDE4) with an IC50 of 2 μM. Etazolate hydrochloride is a γ-aminobutyric acid A (GABAA) receptor regulator. Etazolate hydrochloride is an α-secretase activator and induced the production of soluble amyloid precursor protein (sAPPα). Etazolate hydrochloride, a pyrazolopyridine class derivative, increases cAMP levels. Etazolate hydrochloride has anxiolyticlike, antidepressant-like and anti-inflammatory effects[1][2][3][4][5].
Cipepofol-d6-2 (Ciprofol-d6-2; HSK3486-d6-2) is deuterium labeled Cipepofol (HY-116152). Cipepofol (HSK3486), a psychomotor stabilizing agent, is a gamma-aminobutyric acid (GABA) receptor potentiator.
(R)-Baclofen Hcl(STX-209 Hcl) is a derivative of gamma-aminobutyric acid (GABA) primarily used to treat spasticity and is in the early research stages for use for the treatment of alcoholism.Target: GABABaclofen (brand names Kemstro, Lioresal, Liofen, Gablofen, Beklo and Baclosan) is a derivative of gamma-aminobutyric acid (GABA). It is primarily used to treat spasticity and is in the early research stages for use for the treatment of alcoholism. It is also used by compounding pharmacies in topical pain creams as a muscle relaxant.It is an agonist for the GABAB receptors. Its beneficial effects in spasticity result from actions at spinal and supraspinal sites. Baclofen can also be used to treat hiccups, and has been shown to prevent rises in body temperature induced by the drug MDMA in rats.In addition, research has shown baclofen to be effective in the treatment of alcohol dependence and withdrawal, by inhibiting both withdrawal symptoms andcravings.
Cipepofol-d6 (Ciprofol-d6; HSK3486-d6) is deuterium labeled Cipepofol (HY-116152). Cipepofol (HSK3486), a psychomotor stabilizing agent, is a gamma-aminobutyric acid (GABA) receptor potentiator.
Lesogaberan (AZD-3355) napadisylate 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].
L-838417 is a selective partial agonist at the α2, α3 and α5 subtypes of the GABAA receptor and an antagonist at the α1, with binding Ki values of 0.79 nM, 0.67 nM, 1.67 nM, 267 nM, 2.25 nM and 2183 nM for α1β3γ2, α2β3γ2, α3β3γ2, α4β3γ2, α5β3γ2 and α6β3γ2[1].
PF 0713, a GABAA receptor agonist, is used as an intravenous sedative-hypnotic for general anaesthesia, ICU sedation, procedural sedation, chemotherapy.
TPA023B is a potent, α2/α3 subtype-selective GABAA receptor partial agonist with Ki of 2.0 and 1.8 nM, does not affect the functioning of the α1 subtype; demonstrates anxiolytic effects in rodent and primate models of anxiety, with no significant effects in ataxia and/or myorelaxation.
LAU159 is a functionally selective positive modulator of α1β3 GABA(A) receptor with an EC50 of 2.2 μM[1].
17β-Estradiol sulfate (sodium), also known as β-Estradiol 3-sulfate sodium salt, is a neuroactive steroid[1][2].
Riluzole hydrochloride is an anticonvulsant drug and belongs to the family of use-dependent Na+ channel blocker which can also inhibit GABA uptake with an IC50 of 43 μM.
FG 7142 (ZK 39106; LSU-65), a non-selectively benzodiazepine inverse agonist, has high affinity for the α1 subunit-containing GABAA receptor (Ki=91 nM). FG 7142 (ZK 39106; LSU-65) also modulates GABA-induced chloride flux at GABAA receptors expressing the α1 subunit (EC50= 137 nM). FG 7142 (ZK 39106; LSU-65) can increase tyrosine hydroxylation and cause upregulation of β-adrenoceptors in mouse cerebral cortex[1].
MRK-623 is a potent, α2/α3 subunit functionally selectiviie GABAA receptor agonist.
Gaboxadol hydrochloride (Lu 02-030 hydrochloride) is a selective agonist at GABAA receptors that contain α4-δ subunits, and has anxiolytic and sedative effects[1].
Phenibut (β-Phenyl-GABA) hydrochloride is an orally active GABA-B agonist[1]. Phenibut hydrochloride acts as a GABA-mimetic, primarily at GABAB receptors. Phenibut hydrochloride has anxiolytic and nootropic (cognition enhancing) effects[2].
Tiagabine(NO328) is a selective gamma-aminobutyric acid (GABA) reuptake inhibitor.Target: GABA reuptake inhibitorTiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week 1 (observed cases, p < .05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. Tiagabine may be a useful treatment option for adult patients diagnosed with GAD [1]. Tiagabine was generally well tolerated; the most common adverse events were nausea, dizziness and headaches [2]. Tiagabine (0.1 microM), an antiepileptic drug that specifically inhibits the GAT-1 GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures [3].
AZD7325 is a potent and orally active partial selective PAM of GABAAα2 and Aα3 receptor (Ki=0.3 and 1.3 nM, respectively), and has less antagonistic efficacy at the Aα1 and Aα5 receptor subtypes[1][4]. AZD7325 is a moderate CYP1A2 and a potent CYP3A4 inducer in vitro[2]. AZD7325 has the potential for the investigation of anxiety and dravet syndrome[3]. PAM: positive allosteric modulator.
GABAA receptor agent 1 is a high affinity ligand for GABAA receptor, with potent anticonvulsant activity[1].
(-)-Borneol has a highly efficacious positive modulating action at GABA receptor with an EC50 of 237 μM.
Propanidid (Sombrevin; Fabantol) is a γ-aminobutyric acid type A (GABAA) receptor agonist and a short-acting non-barbiturate general anesthetic agent. Propanidid can decrease the arterial pressure[1][2].
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].
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].
(+)-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].