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Lena-Maria Mehling, Xin Wang, Sys-Stybe Johansen, Annika Spottke, Anna Heidbreder, Peter Young, Burkhard Madea, Cornelius Hess
Gamma-hydroxybutyric acid (GHB) can be used as a knock-out drug in drug facilitated crime (DFC). Due to its rapid metabolism and resulting narrow detection window, uncovering GHB use in DFC still constitutes a problem. In this experiment we determined the GHB and GHB-β-O-glucuronide (GHB-Gluc) concentrations in hair samples after single and chronic GHB exposures. Hair samples of three narcoleptic patients therapeutically taking sodium oxybate (GHB-sodium-salt) were collected. Patients 1 (P1) and 2 (P2) took the medication for nine and six years, respectively...
September 2017: Forensic Science International
Emily C Barker, Michelle Puchowicz, John Letterio, Kristine Higgins, Katherine M Sharkey
OBJECTIVE: To determine GHB levels in breast milk of women taking sodium oxybate (Xyrem) for treatment of narcolepsy and cataplexy. METHODS: Two women with narcolepsy and cataplexy treated with sodium oxybate before pregnancy collected breast milk for analysis of GHB concentration after resuming sodium oxybate postpartum. One woman collected samples across two consecutive nights (doses: 3.0 gm and 4.5 gm twice per night) five months after delivering her first child; the other collected samples on three separate days (doses: 2...
August 2017: Sleep Medicine
Geert Mayer, Andrea Rodenbeck, Karl Kesper
AIMS: To estimate the effect of the compound sodium oxybate (SO) on chin muscle tone in sleep, a re-analysis of the results of the international multicenter study SXB-15 was performed, applying a validated semi-automatic analysis of muscle tone. This analysis distinguishes short (<0.5 s) and long (>0.5 s) muscle activity indices per hour (SMI, LMI) in 116 patients with narcolepsy-cataplexy. While stable stimulant medication was permitted, tricyclics and SSRIs were withdrawn. Polysomnographies were performed at baseline (V5), four weeks after titration of SO to 4...
July 2017: Sleep Medicine
Roberta Tittarelli, Simona Pichini, Daniel S Pedersen, Roberta Pacifici, Monica Moresco, Fabio Pizza, Francesco Paolo Busardò, Giuseppe Plazzi
Sodium oxybate (Xyrem® ), the sodium salt of γ- hydroxybutyric acid (GHB), is a first-line treatment of the symptoms induced by type 1 narcolepsy (NT1) and it is highly effective in improving sleep architecture, decreasing excessive daytime sleepiness and the frequency of cataplexy attacks. Using an ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) validated method, GHB was determined together with its glucuronide (GHB-gluc), in plasma and cerebrospinal fluid (CSF) samples of NT1 patients under sodium oxybate treatment...
May 2017: Forensic Science International
Anna F Rumbach, Andrew Blitzer, Steven J Frucht, Kristina Simonyan
OBJECTIVES/HYPOTHESIS: Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. STUDY DESIGN: Open-label study. METHODS: We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem), an oral agent with therapeutic effects similar to those of alcohol in these patients...
June 2017: Laryngoscope
Alan D Brailsford, Christiaan Bartlett, Andrew T Kicman, David A Cowan
The administration of gamma-hydroxybutyrate (GHB) has been reported to augment the increase in growth hormone (GH) secretion associated with the onset of sleep. The ability of GHB to stimulate GH production in the absence of sleep in both male and female volunteers was investigated as part of a GHB administration study. Twelve healthy volunteers (six men and six women) were given a small oral dose (25 mg/kg) of GHB (as Xyrem(®)) at 10:00 h. Basal blood samples (as serum) were taken 10 min prior to GHB administration, with additional samples taken at 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 240, 360 and 480 min post-administration...
January 2017: Journal of Analytical Toxicology
Michel Maitre, Christian Klein, Ayikoe G Mensah-Nyagan
Gamma-hydroxybutyrate (GHB or Xyrem(R)) is frequently used in humans for several clinical indications, including anesthesia, narcolepsy/cataplexy, and alcohol-withdrawal symptoms. Pharmacological effects induced in the brain by therapeutic doses of Xyrem(R) are generally GABAergic-dependent. These effects allow sedation, stress/anxiety reduction, deep sleep induction, decrease of neuroinflammation, and neuroprotection. Furthermore, Xyrem(R) promotes the expression of pivotal genes reducing toxic proteinopathies, as demonstrated in laboratory animal models...
September 6, 2016: Alzheimer's Research & Therapy
Francesco Paolo Busardò, Elisabetta Bertol, Giulio Mannocchi, Roberta Tittarelli, Flaminia Pantano, Fabio Vaiano, Giovanni Baglio, Chrystalla Kyriakou, Enrico Marinelli
The sodium salt of GHB or sodium oxybate is approved and registered in some countries as a therapeutic substance (Xyrem(®)) for the treatment of narcolepsy-associated cataplexy. This study was designed to measure the GHB endogenous levels in blood and breast milk of 20 breastfeeding women. In addition, blood and breast milk samples of a 32-year-old narcoleptic nursing mother, who was on sodium oxybate treatment, were simultaneously collected at 0.5, 1, 3, 4 and 5h following a 4.5g GHB dose and analyzed, in order to establish the safety interval of time to breastfeed...
August 2016: Forensic Science International
Michel Maitre, Christian Klein, Ayikoe G Mensah-Nyagan
γ-Hydroxybutyrate (GHB) is both a natural brain compound with neuromodulatory properties at central GABAergic synapses (micromolar concentration range) and also a drug (Xyrem(R) ) clinically used for the treatment of various neurological symptoms (millimolar dose range). However, this drug has abuse potential and can be addictive for some patients. Here, we review the basic mechanistic role of endogenous GHB in brain as well as the properties and mechanisms of action for therapeutic clinical doses of exogenous GHB...
May 2016: Medicinal Research Reviews
Francesco P Busardò, Alan W Jones
The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA)...
January 2015: Current Neuropharmacology
Christian Klein, Chantal Mathis, Géraldine Leva, Christine Patte-Mensah, Jean-Christophe Cassel, Michel Maitre, Ayikoe G Mensah-Nyagan
The chronic decrease of brain amyloid-β (Aβ) peptides is an emerging therapeutic for Alzheimer's disease, but no such treatment has achieved clinical validation yet. In vivo, some brain proteases, including neprilysin, possess the ability of degrading Aβ and experimental data suggest their exploitation in strategies to reduce cerebral Aβ concentration. Previous studies have shown that pharmacologic doses of gamma-hydroxybutyrate (sodium oxybate or Xyrem) induce histone deacetylases (HDACs) inhibition and neprilysin gene expression...
February 2015: Neurobiology of Aging
Kristina Simonyan, Steven J Frucht
BACKGROUND: Symptoms of spasmodic dysphonia (SD) are usually managed successfully with botulinum toxin injections. Vocal tremor (VT), which accompanies SD, has a poor response to this treatment. CASE REPORT: We report a case of a female with SD and VT who became symptom-free for 10 months after the intake of a single dose of sodium oxybate (Xyrem®). The long-term treatment effect correlated with attenuated brain activity in the key regions of dystonic brain network...
2013: Tremor and Other Hyperkinetic Movements
Erik J Kaestner, John T Wixted, Sara C Mednick
Sleep affects declarative memory for emotional stimuli differently than it affects declarative memory for nonemotional stimuli. However, the interaction between specific sleep characteristics and emotional memory is not well understood. Recent studies on how sleep affects emotional memory have focused on rapid eye movement sleep (REM) but have not addressed non-REM sleep, particularly sleep spindles. This is despite the fact that sleep spindles are implicated in declarative memory as well as neural models of memory consolidation (e...
October 2013: Journal of Cognitive Neuroscience
Sara C Mednick, Elizabeth A McDevitt, James K Walsh, Erin Wamsley, Martin Paulus, Jennifer C Kanady, Sean P A Drummond
An important function of sleep is the consolidation of memories, and features of sleep, such as rapid eye movement (REM) or sleep spindles, have been shown to correlate with improvements in discrete memory domains. Because of the methodological difficulties in modulating sleep, however, a causal link between specific sleep features and human memory consolidation is lacking. Here, we experimentally manipulated specific sleep features during a daytime nap via direct pharmacological intervention. Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep compared with placebo and sodium oxybate (Xyrem)...
March 6, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ann-Sofie M E Ingels, Katrien B Hertegonne, Willy E Lambert, Christophe P Stove
BACKGROUND: Gamma-hydroxybutyric acid (GHB), well known as a party drug, especially in Europe, is also legally used (sodium oxybate, Xyrem(®)) to treat a rare sleep disorder, narcolepsy with cataplexy. This exploratory study was set up to measure GHB concentrations in dried blood spots (DBS) collected by narcoleptic patients treated with sodium oxybate. Intra- and inter-individual variation in clinical effects following sodium oxybate administration has been reported. The use of DBS as a sampling technique, which is stated to be easy and convenient, may provide a better insight into GHB concentrations following sodium oxybate intake in a real-life setting...
March 2013: CNS Drugs
Geert Mayer
Narcolepsy is a life-long neurodegenerative disorder that causes considerable impairment to quality of life. Until the 1970s, the treatment for one of the main symptoms, excessive daytime sleepiness, was restricted to stimulants, whereas the second core symptom, cataplexy, was treated with antidepressants, and the resultant fragmented night-time sleep with hypnotics. Sodium oxybate (Xyrem(®), UCB Pharma, Brussels, Belgium) is an efficacious drug for all three symptoms which improves the quality of life of narcoleptic patients...
May 2012: Expert Review of Neurotherapeutics
Sarah Hartley, Maria-Antonia Quera-Salva, Mourad Machou
Sodium oxybate (GHB, Xyrem, Jazz Pharmaceuticals) is used to treat cataplexy in patients with narcolepsy. We report the case of a middle aged, normo-ponderal narcoleptic woman without risk factors who developed reversible sleep apnea and objective sleepiness when treated by sodium oxybate, with an apnea-hypopnea index (AHI) of 19.7 on sodium oxybate and AHI 4.8 without treatment. Despite a subjective improvement in vigilance, mean sleep latency on MWT decreased from 21 minutes to 8 minutes on sodium oxybate...
December 15, 2011: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
Jody Langford, William L Gross
Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication...
December 15, 2011: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
François Marclay, Christophe Saudan, Julie Vienne, Mehdi Tafti, Martial Saugy
γ-Hydroxybutyric acid (GHB) is an endogenous short-chain fatty acid popular as a recreational drug due to sedative and euphoric effects, but also often implicated in drug-facilitated sexual assaults owing to disinhibition and amnesic properties. Whilst discrimination between endogenous and exogenous GHB as required in intoxication cases may be achieved by the determination of the carbon isotope content, such information has not yet been exploited to answer source inference questions of forensic investigation and intelligence interests...
May 2011: Analytical and Bioanalytical Chemistry
R Poryazova, S Tartarotti, R Khatami, C R Baumann, P Valko, U Kallweit, E Werth, C L Bassetti
Sodium oxybate (SO; Xyrem®) has been approved in most countries for treatment of narcolepsy and cataplexy. In this study, we present a single-center experience of a series of 18 patients with narcolepsy with cataplexy (18/18 DQB1*0602 positive, 17/17 with low/absent cerebrospinal fluid hypocretin) in whom SO was prescribed. After 26 ± 13 months, 13/18 patients were still on SO at a mean dosage of 6.1 ± 1.2 g (in 8 of them in combination with stimulants). The following significant effects were observed: improved subjective sleepiness (12/13), cataplexy (13/13; median number of attacks from 20 to 1/month), hallucinations (8/10) and sleep paralysis (8/8); increase in mean sleep latency on the Maintenance of Wakefulness Test (from 5...
2011: European Neurology
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