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γ-Hydroxybutyrate/Sodium Oxybate

Neurobiology, and Impact on Sleep and Wakefulness

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Abstract

γ-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations.

Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABAB receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO2 and H2O through the tricarboxylic acid cycle (Krebs cycle).

Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to nighttime sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

  2. In this section, the term sodium oxybate has been used only when referring to the branded product, Xyrem™.

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Acknowledgements

Mr Pardi is an employee of and owns stock/options for Jazz Pharmaceuticals, the distributor of sodium oxybate. Dr Black has served as a principal investigator for studies supported by Cephalon and Jazz Pharmaceuticals and has also provided consulting services for Cephalon and Jazz Pharmaceuticals.

No outside funding was used in the preparation of this review.

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    Daniel Pardi

  2. Stanford University, 401 Quarry Road, Ste 3301 MC 5730, Stanford, California, 94305-5730, USA

    Jed Black

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Pardi, D., Black, J. γ-Hydroxybutyrate/Sodium Oxybate. CNS Drugs 20, 993–1018 (2006). https://doi.org/10.2165/00023210-200620120-00004

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