Disease relevance of Sodium oxybate

• The protective effect of gamma-hydroxybutyrate in regional intestinal ischemia in the hamster [1].
• Hydroxybutyrate administration did not significantly affect the rate of weight-loss but seemed to increase the fat/lean ratio of the tissue loss [2].
• Inherited succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria) is one of the few neurogenetic disorders of GABA metabolism, and one in which tonic-clonic seizures associate with increased central nervous system GABA and gamma-hydroxybutyrate (GHB) [3].
• A novel gamma-hydroxybutyrate dehydrogenase: identification and expression of an Arabidopsis cDNA and potential role under oxygen deficiency [4].
• Life-threatening interactions between HIV-1 protease inhibitors and the illicit drugs MDMA and gamma-hydroxybutyrate [5].

Psychiatry related information on Sodium oxybate

• Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men [6].
• gamma-Hydroxybutyrate in narcolepsy [7].
• Gamma-hydroxybutyrate dependence with social phobia [8].
• "Grievous bodily harm:" gamma hydroxybutyrate abuse leading to a Wernicke-Korsakoff syndrome [9].
• BACKGROUND: Exogenous gamma-hydroxybutyrate (GHB) increases slow-wave sleep and reduces daytime sleepiness and cataplexy in patients with primary narcolepsy [10].

High impact information on Sodium oxybate

• After reports of toxic effects of gamma-hydroxybutyrate and its resultant regulation by the federal government, 1,4-butanediol and gamma-butyrolactone, another precursor of gamma-hydroxybutyrate and an industrial solvent, began to be marketed as dietary supplements [11].
• BACKGROUND: 1,4-Butanediol is an industrial solvent that, when ingested, is converted to gamma-hydroxybutyrate, a drug of abuse with depressant effects, primarily on the central nervous system [11].
• We used gas chromatography-mass spectrometry to measure 1,4-butanediol or its metabolite, gamma-hydroxybutyrate, in urine, serum, or blood [11].
• The aim of this study was to investigate, in normal young men, whether gamma-hydroxybutyrate (GHB), a reliable stimulant of slow-wave (SW) sleep in normal subjects, would simultaneously enhance sleep related growth hormone (GH) secretion [6].
• Treatment with gamma-hydroxybutyrate after ischemia but before reperfusion also provided significant protection [1].

Chemical compound and disease context of Sodium oxybate

• The effect of gamma-hydroxybutyrate (GHB) on the reactivity of pial arteries to local metabolic factors was tested in chloralose-anesthetized cats before or after a period of transient ischemia induced by air embolism [12].
• RESULTS: The main chemicals causing brain death of the donor were carbon monoxide (n=4), cocaine (n=4), tricyclic antidepressants (n=3), 3,4-methylenedioxy- methamphetamine (n=2), opiates (n=2), aspirin (n=1), gamma hydroxybutyrate (n=1), heroin (n=1), insulin (n=1), verapamil (n=1), barbiturate (n=1), and brompheniramine/phenylpropanolamine (n=1) [13].
• The gamma-hydroxybutyrate model of absence seizures: correlation of regional brain levels of gamma-hydroxybutyric acid and gamma-butyrolactone with spike wave discharges [14].
• Hypothermia in response to l-baclofen (6 and 12 mg/kg) or GHB (1 g/kg), baclofen-induced ataxia as determined on the fixed-speed Rotarod, and GHB-induced hypolocomotion were significantly, but for the most part similarly, attenuated in both GABA(B(1a))(-/-) and GABA(B(1b))(-/-) mice [15].
• A new coenzyme A (CoA)-transferase from the anaerobe Clostridium aminobutyricum catalyzing the formation of 4-hydroxybutyryl-CoA from 4-hydroxybutyrate and acetyl-CoA is described [16].

Biological context of Sodium oxybate

• The kinetics of the oxidation of gamma-hydroxybutyrate have been studied in both the uncoupled and the coupled reaction [17].
• Gamma-hydroxybutyrate reduces mitogen-activated protein kinase phosphorylation via GABA B receptor activation in mouse frontal cortex and hippocampus [18].
• It is proposed that GHBDH and SSADH activities in plants are regulated in a complementary fashion and that GHBDH and gamma-hydroxybutyrate function in oxidative stress tolerance [4].
• Also, GHB directly hyperpolarized layer 2/3 non-pyramidal cells by up to 11 mV and inhibited action potential firing [19].
• In conclusion, GHB activates both pre- and postsynaptic GABA(B)-receptors in neocortical neurons participating in fast synaptic transmission, leading to a powerful depression of neocortical network activity [19].

Anatomical context of Sodium oxybate

• However, in the hippocampus and the frontal cortex, it seems that gamma-hydroxybutyrate induces depolarization with an accumulation of cGMP and an increase in inositol phosphate turnover [20].
• Neuronal depolarization releases gamma-hydroxybutyrate into the extracellular space in a Ca(2+)-dependent manner [20].
• Using minimal stimulation, GHB reduced the probability of release at inhibitory synapses onto neocortical layer 2/3 pyramidal cells [19].
• RESULTS: A 2-day and 10-day gamma-hydroxybutyrate administration decreased the spontaneous firing activity of locus coeruleus neurons by 52% and 54%, respectively, when compared with controls [21].
• Blood and cerebrospinal fluid samples were assayed for gamma hydroxybutyrate [22].

Associations of Sodium oxybate with other chemical compounds

• Kinetics of coupled gamma-hydroxybutyrate oxidation and D-glucuronate reduction by an NADP+-dependent oxidoreductase [17].
• At 0.5 h exposure the right cerebral hemisphere of animals receiving Krebs', GHB or GBL showed equivalent decreases of ATP and phosphocreatine and increase of ADP, AMP and lactate which indicated that these depressant drugs had no beneficial effect on the energy metabolism of the acutely hypoxic-oligemic brain [23].
• Fasting 1/2, 1, and 2 h postprandial values for insulin, glucagon, glucose, lactate, beta hydroxybutyrate, acetoacetate, and free fatty acids were assessed before and the 1st, 3rd, and 5th day after immunization [24].
• Effects of sustained gamma-hydroxybutyrate treatments on spontaneous and evoked firing activity of locus coeruleus norepinephrine neurons [21].
• Conversion of gamma-hydroxybutyrate to gamma-aminobutyrate in vitro [25].

Gene context of Sodium oxybate

• Human DHRS6 is a previously uncharacterized member of the short chain dehydrogenases/reductase family and displays significant homologies to bacterial hydroxybutyrate dehydrogenases [26].
• Pharmacological profiles of generalized absence seizures in lethargic, stargazer and gamma-hydroxybutyrate-treated model mice [27].
• Lactate dehydrogenase, hydroxybutyrate dehydrogenase and gamma-glutamyltransferase activities did not change significantly [28].
• Two other genes (orf1 and orf6) conferring utilization of 4-hydroxybutyrate were identified during subcloning and sequencing of the inserts of pAH1 and pAH3 [29].
• From analysis of each tumor marker the greatest positive results were obtained with the markers beta 2-microglobulin (57.1%), lactate dehydrogenase (53.1%), and hydroxybutyrate dehydrogenase (46.2%) for patients with carcinoma of the ovary [30].

Analytical, diagnostic and therapeutic context of Sodium oxybate

• Naloxone overcomes the dopaminergic, EEG, and behavioral effects of gamma-hydroxybutyrate [31].
• The efficacy of gamma-hydroxybutyrate (GHB) versus placebo for treating narcolepsy was evaluated in 20 patients with narcolepsy, 10 men and 10 women, using a double-blind counterbalanced crossover design [32].
• Extracellular events induced by gamma-hydroxybutyrate in striatum: a microdialysis study [33].
• The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study [34].
• The effects of acute and repeated gamma-hydroxybutyrate (GHB) and cocaine administration on D1 and D2 dopamine receptor mRNA expression were examined using in situ hybridization histochemistry in different rat brain structures rich in GHB receptors [35].

References