更新于：2024-11-01

GHB receptor x GABA transaminase

更新于：2024-11-01

基本信息

关联

项与 GHB receptor x GABA transaminase 相关的药物

UMB86

靶点

GABA transaminase x GHB receptor

作用机制

GABA transaminase agonists [+1]

在研机构

The University of Texas System

原研机构

The University of Texas System

在研适应症

发作性睡病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GHB receptor x GABA transaminase 相关的临床结果

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100 项与 GHB receptor x GABA transaminase 相关的转化医学

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0 项与 GHB receptor x GABA transaminase 相关的专利（医药）

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项与 GHB receptor x GABA transaminase 相关的文献（医药）

2009-01-20·Neurology1区 · 医学

γ-Hydroxybutyric acid and its relevance in neurology

1区 · 医学

Article

作者: Benarroch, Eduardo E

ACh = acetylcholine; AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; DA = dopamine; EDS = excessive daytime sleepiness; GABA = γ-aminobutyric acid; GABA-T = GABA transaminase; GAD = glutamic acid decarboxylase; GBL = γ-butyrolactone; GH = growth hormone; GHB = γ-hydroxybutyric acid; GHBDH = GHB dehydrogenase; GIRK = G-protein-coupled inward rectifying K+ channels; 5-HT = serotonin; NADPH = nicotinamide adenine dinucleotide phosphate; NMDA = N -methyld-aspartate; SSA = succinic semialdehyde; SSADH = succinic semialdehyde dehydrogenase deficiency; SSAR = succinic semialdehyde reductase; VGCC = voltage-gated Ca2+ channels; VIAAT = vesicular inhibitory amino acid transporter; VTA = ventral tegmental area. γ-Hydroxybutyric acid (GHB, oxybate) is formed from γ-aminobutyric acid (GABA) in the normal human brain. GHB can also be administered exogenously and readily passes the blood–brain barrier. In the brain, GHB may have a widespread neuromodulatory role that is mediated both by GHB-specific and γ-aminobutyric acid type B (GABAB) receptors. There has been widespread interest in GHB as a result of its emergence as a major recreational drug. Exogenously administered GHB elicits intoxication, withdrawal, tolerance, and addiction. GHB also induces slow wave sleep and has now been approved for treatment of narcolepsy. GHB may also have limited use as an anesthetic and in alcohol dependence and withdrawal. Accumulation of GHB may underlie some of the manifestations of succinic semialdehyde dehydrogenase deficiency (SSADH) in humans. The development of a murine model of this disease, together with that of specific GHB receptor ligands, has provided insights into the physiologic role of GHB in the brain and rationale for therapeutic intervention in neurologic disorders. These subjects have all been extensively reviewed.1–8 GHB is present in the normal brain and serves as both a precursor and a degradation product of GABA1–4 (figure). GABA is formed from glutamate by action of the glutamic acid …

1997-05-01·The Journal of pharmacology and experimental therapeutics

gamma-Hydroxybutyrate conversion into GABA induces displacement of GABAB binding that is blocked by valproate and ethosuximide.

Article

作者: Maitre, M ; Ratomponirina, C ; Hechler, V

gamma-Hydroxybutyrate (GHB) has been reported to be a ligand for GABAB receptor(s), although with low or very low affinity (IC50 = 150-796 microM). In addition, several reports argue for a role of GHB via GABAB receptors in both in vivo and in vitro electro-physiological experiments. In the present study, we demonstrate that the inhibition of GHB's conversion into GABA by rat brain membranes blocks the ability of GHB to interfere with GABAB binding. In particular, the inhibition of GHB dehydrogenase by valproate or ethosuximide and the blockade of GABA-T by aminooxyacetic acid induce the disappearance of the GABA-like effect of GHB at GABAB, but also at GABAA, receptors. This finding could explain the misinterpretation of in vitro or in vivo experiments where GHB possesses a GABA-like effect. But in addition, it is postulated that the normal metabolism of GHB in brain induces GABAB mechanisms that could be blocked by the administration of valproate or ethosuximide.

1985-10-07·FEBS Letters3区 · 生物学

Evidence for a role of high K_m aldehyde reductase in the degradation of endogenous γ‐hydroxybutyrate from rat brain

3区 · 生物学

Article

作者: Philippe Vayer ; Michel Maitre ; Martine Schmitt ; Jean-Jacques Bourguignon ; Paul Mandel

γ‐Hydroxybutyrate (GHB) is a putative neurotransmitter in brain. We have already demonstrated that it is transformed into γ‐aminobutyrate (GABA) by rat brain slices incubated under physiological conditions. This conversion occurs via a GABA‐transaminase reaction. Therefore, succinic semialdehyde, the oxidative derivative of GHB, appears to be the primary catabolite of GHB degradation. Apparently, the kinetic characteristics and pH optimum of GHB dehydrogenase (high Km, aldehyde reductase) in vitro do not favor a role for this enzyme in endogenous brain GHB oxidation. However, in the presence of glucuronate, glutamate, NADP and pyridoxal phosphate, pure GHB dehydrogenase, coupled to purified GABA‐transaminase does produce GABA from GHB at an optimum pH close to the physiological value and with a low Km for GHB.