Skip to main content
Springer Nature Link
Log in

Gamma-Hydroxybutyrate (Sodium Oxybate): From the Initial Synthesis to the Treatment of Narcolepsy–Cataplexy and Beyond

  • Chapter
  • First Online:
Save chapter
View saved research
Sleep Medicine

Abstract

Laborit synthesized GHB in the 1960s hoping t would be a precursor for gamma-aminobutyric acid. He found it had unique pharmacological and metabolic effects. GHB was later used totreat sleep-related disorders. In depression GHB could induce sleep-onset REM sleep and even sleep paralysis. In narcolepsyit improved night sleep quality and reduced daytime sleepiness andcataplexy without development of tolerance or significant side effects. Later reports have shown positive clinical effects in Parkinson's disease, chronic fatigue syndrome and fibromyalgia.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
eBook
USD 119.00
Price excludes VAT (USA)
Softcover Book
USD 159.99
Price excludes VAT (USA)
Hardcover Book
USD 219.99
Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  1. Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders. meta-analysis. Arch Gen Psychiatry. 1992;49(8):651–68.

    Article  CAS  PubMed  Google Scholar 

  2. Charney DS, Mihic SJ, Harris RA. Hypnotics and sedatives. In: Brunton LL, Lazo JS, Parker KL, editors. The pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill; 2006. pp. 401–23.

    Google Scholar 

  3. Laborit H-M. Sodium-4-hydroxybutyrate. Int J Neuropharmacol. 1964;3:433–52.

    Article  CAS  PubMed  Google Scholar 

  4. Laborit H, Jouany JM, Gerard J, Fabiani F. Generalities concerning the experimental study and clinical use of gamma hydroxybutyrate of Na [Article in French]. Agressologie. 1960;1:387–406.

    Google Scholar 

  5. Muyard J, Laborit H-M. Gammahydroxybutyrate psychotherapeutic drugs: Part-II. In: Usdin E, Forrest J, editors. Applications: psychopharmacology. New York: Marcel-Dekker; 1977. pp. 1339–75.

    Google Scholar 

  6. Roth RH, Giarman NJ. Conversion in vivo of gamma-aminobutyric to gamma-hydroxybutyric acid in the rat. Biochem Pharmacol. 1969;18(1):247–50.

    Article  CAS  PubMed  Google Scholar 

  7. Vickers MD. Gammahydroxybutyric acid. Int Anesthesiol Clin. 1969;7(1):75–89.

    Article  CAS  PubMed  Google Scholar 

  8. Mamelak M, Escriu JM, Stokan O. The effects of gamma-hydroxybutyrate on sleep. Biol Psychiatry. 1977;12(2):273–88.

    CAS  PubMed  Google Scholar 

  9. Godbout R, Montplaisir J. Effects of γ-hydroxybutyrate on sleep. In: Tunnicliff G, Cash CD, editors. Gammahydroxybutyrate: molecular, functional and clinical aspects. London: Taylor and Francis; 2002. pp. 120–32.

    Google Scholar 

  10. Mamelak M, Escriu JM, Stokan O. Sleep-inducing effects of gammahydroxybutyrate. Lancet. 1973;2(7824):328–9.

    Article  CAS  PubMed  Google Scholar 

  11. Nishino S, Kanbayashi T. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med Rev. 2005;9(4):269–310.

    Article  PubMed  Google Scholar 

  12. Sakurai T. Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Med Rev. 2005;9(4):231–41.

    Article  PubMed  Google Scholar 

  13. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat. Rev. Neurosci. 2007;8:171–81.

    Article  CAS  PubMed  Google Scholar 

  14. Broughton R, Valley V, Aguire M, Roberts J, Suwalski W, Dunham W. Excessive daytime sleepiness and the pathophysiology of narcolepsy-cataplexy: a laboratory perspective. Sleep 1986;9(1):205–15.

    CAS  PubMed  Google Scholar 

  15. Broughton R, Dunham W, Weiskopf M, Rivers M. Night sleep does not predict day sleep in narcolepsy. Electroenceph Clin Neurophysiol. 1994;91:67–70.

    Article  CAS  PubMed  Google Scholar 

  16. Broughton RJ, Krupa S, Boucher B, Rivers M, Mullington J. Impaired circadian waking arousal in narcolepsy-cataplexy. Sleep Res Online. 1998;1(4):159–65. http://www.sro.org/1988/broughton/159/.

    CAS  PubMed  Google Scholar 

  17. Broughton R, Mamelak M. Gamma-hydroxy-butyrate in the treatment of compound narcolepsy. Sleep Res. 1975;4:211.

    Google Scholar 

  18. Hoddes E, Zarcone V, Smythe H, Philips R, Dement WC. Quantification of sleepiness: a new approach. Psychophysiol. 1973;10:431–6.

    Article  CAS  Google Scholar 

  19. Broughton R, Mamelak M. Gammahydroxybutyrate in the treatment of narcolepsy: a preliminary report. In: Guillemmault C, Dement WC, Passouant P, editors. Narcolepsy. Advances in sleep research. New York: Spectrum; 1976. pp. 659–67.

    Google Scholar 

  20. Broughton R, Mamelak M. The treatment of narcolepsy-cataplexy with nocturnal gamma-hydroxybutyrate. Can J Neurol Sci. 1979;6(1):1–6.

    CAS  PubMed  Google Scholar 

  21. Broughton R, Mamelak M. Effects of nocturnal gamma-hydroxybutyrate on sleep/waking patterns in narcolepsy-cataplexy. Can J Neurol Sci. 1980;7(1):23–31.

    CAS  PubMed  Google Scholar 

  22. Lammers GJ, Arends J, Declerck AC, Ferrari MD, Schouwink G, Troost J. Gammahydroxybutyrate and narcolepsy: a double-blind placebo-controlled study. Sleep. 1993;16(3):216–20.

    CAS  PubMed  Google Scholar 

  23. Scrima L, Hartman PG, Johnson FH Jr, Hiller FC. Efficacy of gamma-hydroxybutyrate versus placebo in treating narcolepsy-cataplexy: double-blind subjective measures. Biol Psychiatry. 1989;26(4):331–43.

    Article  CAS  PubMed  Google Scholar 

  24. Scrima L, Hartman PG, Johnson FH Jr, Thomas EE, Hiller FC. The effects of gamma-hydroxybutyrate on the sleep of narcolepsy patients: a double-blind study. Sleep. 1990;13(6):479–90.

    CAS  PubMed  Google Scholar 

  25. Mamelak M. Narcolepsy and depression and the neurobiology of gammahydroxybutyrate. Prog Neurobiol. 2009;89(2):193–219.

    Article  CAS  PubMed  Google Scholar 

  26. Mamelak M, Scharf MB, Woods M. Treatment of narcolepsy with gamma-hydroxybutyrate. A review of clinical and sleep laboratory findings. Sleep. 1986; 9(1 Pt 2):285–9.

    CAS  PubMed  Google Scholar 

  27. Scharf MB, Brown D, Woods M, Brown L, Hirschowitz J. The effects and effectiveness of gamma-hydroxybutyrate in patients with narcolepsy. J Clin Psychiatry. 1985;46(6):222–5.

    CAS  PubMed  Google Scholar 

  28. Broughton R, Ghanem Q, Hishikawa Y, Sugita Y, Nevsimalova S, Roth B. Life effects of narcolepsy in 180 patients from North-America, Asia and Europe compared to matched controls. Can J Neurol Sci. 1981;8:299–304.

    CAS  PubMed  Google Scholar 

  29. Broughton R, Ghanem Q, Hishikawa Y, Sugita Y, Nevsimalova S, Roth B. Life effects of narcolepsy: relationships to geographic origin (North American, Asian or European and to other patient and illness variables. Can J Neurol Sci. 1983;10:100–4.

    CAS  PubMed  Google Scholar 

  30. Broughton R, Guberman A, Roberts J. Comparison of psychosocial effects of epilepsy and of narcolepsy-cataplexy: a controlled study. Epilepsia. 1984;25:423–33.

    Article  CAS  PubMed  Google Scholar 

  31. Weaver TE, Cuellar N. A randomized trial evaluating the effectiveness of sodium oxybate therapy on quality of life in narcolepsy. Sleep. 2006;29(9):1189–94.

    PubMed  Google Scholar 

  32. US Xyrem Multicenter Study Group. A randomized double blind, placebo controlled multicenter trial comparing the effects of three doses of orally administered sodium oxybate with placebo for the treatment of narcolepsy. Sleep. 2002;25:42–9.

    Google Scholar 

  33. US Xyrem Multicenter Study Group. A 12 month, open label, multicenter extension trial of orally administered sodium oxybate for the treatment of narcolepsy. Sleep. 2003;26:31–5.

    Google Scholar 

  34. US Xyrem Multicenter Study Group. Sodium oxybate demonstrates long term efficacy for the treatment of cataplexy in patients with narcolepsy. Sleep Med. 2004;5:119–23.

    Article  Google Scholar 

  35. Martinez-Rodriguez J, Iranzo A, Santamaria J, Genis D, Molins A, Silva Y, et al. Status cataplecticus induced by abrupt withdrawal of clomipramine. Neurologia. 2002;17(2):113–6.

    PubMed  CAS  Google Scholar 

  36. Mamelak M, Black J, Montplaisir J, Ristanovic R. A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy. Sleep. 2004;27(7):1327–34.

    PubMed  Google Scholar 

  37. Mitler MM, Gujavarty S, Browman CP. Maintenance of wakefulness test: a polysomnographic technique for evaluating treatment efficacy in patients with excessive somnolence. Electroenceph Clin Neurophysiol. 1982;53:658–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Johns MW. A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 1991;14:540–5.

    CAS  PubMed  Google Scholar 

  39. Xyrem International Study Group. Further evidence supporting the use of sodium oxybate for the treatment of cataplexy: a double blind placebo-controlled study in 228 patients. Sleep Med. 2005a;6:415–21.

    Article  Google Scholar 

  40. Xyrem International Study Group. A double blind, placebo controlled study demonstrates sodium oxybate is effective for the treatment of excessive daytime sleepiness in narcolepsy. J Clin Sleep Med. 2005b;1:391–7

    Google Scholar 

  41. Black J, Houghton WC. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep 2006;29(7):939–46.

    PubMed  Google Scholar 

  42. Murali H, Kotagal S. Off-label treatment of severe childhood narcolepsy-cataplexy with sodium butyrate. Sleep. 2006;29(8):1025–9.

    PubMed  Google Scholar 

  43. Richardson GS, Carskadon MA, Flagg W, van den Hoed J, Dement WC, Mitler MM. Excessive daytime sleepiness in man: multiple sleep latency measurements in narcoleptic and control subjects. Electroencephalogr Clin Neurophysiol. 1978;45: 621–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Aran A, Einen M, Lin L, Plazzi G, Nishino S, Mignot E. Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a retrospective study of 51 children. Sleep. 2010;33(11):1457–64.

    PubMed Central  PubMed  Google Scholar 

  45. Peraita-Adrados R, Garcia-Peñas JJ, Ruiz-Falco L, Gutiērrez-Solana L, Lopez-Esteban P, Vicario JL, Miano S, Aparicio-Meix M, Martinez-Sopena MJ. Clinical, polysomnographic and laboratory characteristics of narcolepsy-cataplexy in a sample of chidren and adolescents. Sleep Med. 2011;12:24–7. (Epub 2010 Nov 2).

    Article  PubMed  Google Scholar 

  46. Mansukhani MP, Kotagal S. Sodium oxybate in the treatment of childhoon narcolepsy-cataplexy: a retrospective study. Sleep Med. 2012;13(6):606–10. (Epub 2012 Mar 24).

    Article  PubMed  Google Scholar 

  47. Lecendreux M, Poli F, Oudiette D, Benazzouz F, Doniacour CE, Franceschini C, Finotti E, Pizza F, Bruni O, Piazzi G. Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study. Sleep. 2012;35(5):709–11.

    PubMed Central  PubMed  Google Scholar 

  48. George CF, Feldman N, Inhaber N, Steininger TL, Greschik SM, Lai C, Zheng Y. A safety trial of sodium oxybate in patients with obstructive sleep apnea: acute effects on sleep-disordered breathing. Sleep Med. 2010;11(1):38–42.

    Article  PubMed  Google Scholar 

  49. George CF, Feldman N, Zheng Y, Steininger TL, Grzeschik SM, Lai C, Inhaber N. A 2-week, polysomnographic safety trial of sodium oxybate in obstructive sleep apnea syndrome. Sleep Breath. 2011;15(1):13–20. (Epub 2010 Jan 18).

    Article  PubMed Central  PubMed  Google Scholar 

  50. Seeck-Hirschner M, Baier PC, von Freier A, Aldenhoff J, Göder R. Increase in sleep-related breathing disturbances after treatment with sodium oxybate in patients with narcolepsy and mild obstructive sleep apnea syndrome: two case reports. Sleep Med. 2009;10(1):154–5. (Epub 2008 Jan 28).

    Article  CAS  PubMed  Google Scholar 

  51. Moldofsky H. The significance of the sleeping-waking brain for the understanding of the widespread musculoskeletal pain and fatigue in fibromyalgia and allied syndromes. Joint Bone Spine. 2008;75(4):397–402. (Epub 2008 May 5).

    Article  PubMed  Google Scholar 

  52. Russell IJ, Perkins AT, Michalek JE. Oxybate SXB-26 fibromyalgia study group. Arthritis Rheum. 2009;60(1):299–309.

    Article  CAS  PubMed  Google Scholar 

  53. Wallace DM, Maze T, Shafazand S. Sodium oxybate-induced sleep driving and sleep-related eating disorder. J Clin Sleep Med. 2011;7(3):310–1.

    PubMed Central  PubMed  Google Scholar 

  54. Spitzer AR, Broadman M. Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Pract. 2010;10(1):54–9.

    Article  PubMed  Google Scholar 

  55. Moldofsky M, Inhaber NH, Guintya DR, Alvarez-Horine SB. Effects of sodium oxybate on sleep physiology and sleep/wake related symptoms in patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study. J Rheumatol. 2010;37(10):2156–66. (Epub 2010 Aug 3).

    Article  CAS  PubMed  Google Scholar 

  56. Russell IJ, Holman AJ, Swick TJ, Varez-Horine S, Wang YG, Guinta D. Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study. Pain. 2011;152(5):1007–17.

    Article  CAS  PubMed  Google Scholar 

  57. Staud R. Pharmacological treatment of fibromyalgia syndrome: new developments. Drugs. 2010;70(1)1–14.

    Article  CAS  PubMed  Google Scholar 

  58. Staud R. Sodium oxybate for the treatment of fibromyalgia. Expert Opin Pharmacother. 2011;12(11):1789–98. (Epub 2011 June 16).

    CAS  PubMed  Google Scholar 

  59. Crawford BK, Piault EC, Lai C, Bennett RM. Assessing fibromyalgia-related fatigue: content validity and psychometric performance of the fatigue visual analog scale in adult patients with fibromyalgia. Clin Exp Rheumatol. 2011;29(6 Suppl 69):S34–63. (Epub 2012 Jan 3).

    CAS  PubMed  Google Scholar 

  60. Spaeth M, Bennett RM, Benson BA, Wang YG, Lai C, Choy EH. Sodium oxybate therapy provides multidimensional improvement in fibromyalgia: results of an international phase 3 trial. Ann Rheum Dis. 2012;71(6):935–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Boeve BF, Silber MH, Ferman TJ, Kokmen E, Smith GE, Ivnik RJ, Parisi JE, Olson EJ, Petersen RC. REM sleep behaviour disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology. 1998;51(2):363–70.

    Article  CAS  PubMed  Google Scholar 

  62. Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, Benarroch EE, Ahiskog JE, Smith GE, Caselli RC, Tipppman-Peikert M, Olson EJ, Lin S-C, Young T, Wszolek Z, Schenck CH, Mahowald MW, Catillo PR, Del Tredici K, Braak H. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 2007;130:2770–88.

    Article  CAS  PubMed  Google Scholar 

  63. Gagnon J-F, Bédard M-A, Fantini ML, Petit D, Panisset M, Rompré S, Carrier J, Montplaisir J. REM sleep behavior disorder and REM sleep without atonia in Parkinson’s disease. Neurology. 2002;59(4):585–9.

    Article  CAS  PubMed  Google Scholar 

  64. Olson EJ, Boeve BF, Silber MH. Rapid eye movement behavior disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000;123:331–9.

    Article  PubMed  Google Scholar 

  65. Schenck C, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38 % of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 1996;46(2):388–93.

    Article  CAS  PubMed  Google Scholar 

  66. Sixel-Döring F, Trautmann E, Mollenhauer B, Trenkwalder C. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology. 2011;77(11):1048–54.

    Article  PubMed  CAS  Google Scholar 

  67. Shneesen JM. Successful treatment of REM sleep behaviour disorder with sodium oxybate. Clin Neuropharm. 2009;32(3):158–9.

    Article  CAS  Google Scholar 

  68. Arnulf I, Leu-Semenescu S. Sleepiness in Parkinson’s disease. Parkinsonism Relat Disord. 2009;15(Suppl. 3):S101–4.

    Google Scholar 

  69. Ondo WG, Perkins T, Swick T, Hull KL, Jiminez JE, Garrir TS, Pardi D. Sodium oxybate for excessive daytime sleepiness in Parkinson disease. Arch Neurol. 2008;63(10):1337–40.

    Google Scholar 

  70. Gao B, Kilic E, Baumann CR, Hermann DM, Bassetti CL. Gamma-hydroxybutyrate accelerates functional recovery after focal cerebral ischemia. Cerebrovasc Dis. 2008;26(4):413–9. (Epub 2008 Aug 28).

    Article  CAS  PubMed  Google Scholar 

  71. MacMillan V. Effects of gamma-hydroxybutrate and gamma-butyrolactone on cerebral energy metabolism during exposure and recovery from hypoxemia-oligemia. Stroke. 1080;11(3):271–7.

    Google Scholar 

  72. Ottani A, Saltini S, Bartiromo M, Zaffe D, Renzo-Botticelli A, Ferrari A, Bertolini A, Genedani S. Effect of gamma-hydroxybutyrate in two rat models of focal cerebral damage. Brain Res. 2003;986(1/2):181–90.

    Article  CAS  PubMed  Google Scholar 

  73. Sadasivan S, Maher TJ, Quang LS. Gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL) and 1,4-butanedio (1,4-BD) reduce the volume of cerebral infarction in rodent transient middle cerebral artery occlusion. Ann N Y Acad Sci. 2006;1074:537–44

    Article  CAS  PubMed  Google Scholar 

  74. Mamelak M. Alzheimer’s disease, oxidative stress and gammahydroxybutyrate. Neurobiol Aging. 2007;28(9):1340–60. (Epub 2006 Jul 11).

    Article  CAS  PubMed  Google Scholar 

  75. Mamelak M. Sporadic Alzheimer’s disease: the starving brain. J Alzheimers Dis. 2012;31(3):459–74.

    PubMed  Google Scholar 

  76. Husain Am, Ristanovic RK, Bogan RK. Weight loss in narcolepsy patients treated with sodium oxybate. Sleep Med. 2009;10(6):661–3. (Epub 2008 Nov 17).

    Article  PubMed  Google Scholar 

  77. Rossetti AQ, Heinzer RC, Tafti M, Buclin T. Rapid occurrence of depression following addition of sodium oxybate to modafinil. Sleep Med. 2010;11(5):500–1. (Epub 2010 Feb 4).

    Article  PubMed  Google Scholar 

  78. Langford J, Gross WL. Psychosis in the context of sodium oxybate therapy. J Clin Sleep Med. 2011;7(6):665–6.

    PubMed Central  PubMed  Google Scholar 

  79. Bédard MA, Montplaisir J, Godbout R, Lapierre O. Nocturnal gamma-hydroxybutyrate. Effect on periodic leg movements and sleep organization of narcoleptic patients. Clin Neuropharmacol. 1989;12(1):29–36.

    Article  PubMed  Google Scholar 

  80. Poli F, Ricotta L, Vandi S, Franceschini C, Pizza F, Palaia V, Moghadam KK, Banal D, Vetrugno R, Thorpy MJ, Plazzi G. Catathrenia under sodium oxybate in narcolepsy with cataplexy. Sleep Breath. 2012;16(2):427–34. (Epub 2011 Apr 12).

    Article  PubMed  Google Scholar 

  81. Akins BE, Miranda E, Lacy JM, Logan BK. A multi-drug intoxication fatality involving Xyrem (GHB). J Forensic Sci. 2009;54(2):495–6. (Epub 2009 Jan 29).

    Article  PubMed  Google Scholar 

  82. Zvosec DL, Smith SW, Hall BJ. Three deaths associated with use of Xyrem. Sleep Med. 2009;10(4):490–3. (Epub 2009 Mar 9).

    Article  Google Scholar 

  83. Zvosec DL, Smith SW, Porrata T., Strobl AQ, Dyer JE. Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma. Am J Emerg Med. 2011;29(3):319–32.

    Article  Google Scholar 

  84. Lammers GJ, Bassetti C, Billiard M, Black J, Broughton R, Dauvilliers Y, Ferini-Strambi L, Garcia-Borreguero D, Goswami M, Högl B, Iranzo A, Jennum P, Khatami R, Lecendreux M, Mayer G, Mignot E, Montplaisir J, Nevsimalova S, Peraita-Adrados R, Plazzi G, Scammell T, Silber M, Sonka K, Tafti M, Thorpy M. Sodium oxybate is an effective and safe treatment for narcolepsy. Sleep Med. 2010;11:105–8.

    Article  PubMed  Google Scholar 

  85. House of Commons, Science and Technology Committee. Fifth Report of Session 2005–05. 2006. http://news.bbc.co.uk/1/shared/bsp/hi/pdfs/31_07_06_drugsreport.pdf. Accessed 31 Jul 2006.

  86. Xie XS, Pardi D, Black J. Molecular and cellular actions of γ-hydroxybutyric acid: possible mechanisms underlying GHB efficacy in narcolepsy. In: Bassetti CL, Billiard M, Mignot E, editors. Narcolepsy and hypersomnia. New York: Informa Healthcare; 2007. pp. 583–620.

    Google Scholar 

  87. Lapierre O, Montplaisir J, Lamarre M, Bedard MA. The effect of gamma-hydroxybutyrate on nocturnal and diurnal sleep of normal subjects: further considerations on REM sleep-triggering mechanisms. Sleep. 1990;13(1):24–30.

    CAS  PubMed  Google Scholar 

  88. Passouant P. Problemes physiopathologiques de la narcolepsie et periodicité du sommeil rapide au cours du nycthemère. In: Gastaut H, Lugaresi E, Berti Ceroni G, Coccagna G, editors. The abnormalities of sleep in man. Bologna: Aulo Gaggi Editore; 1968. p. 177–190.

    Google Scholar 

  89. Montplaisir J, Godbout R. Nocturnal sleep of narcoleptic patients: revisited. Sleep. 1986; 9(1 Pt 2):159–61.

    CAS  PubMed  Google Scholar 

  90. Van Nieuwenhuijzen PS, McGregor IS, Hunt GE. The distribution of gamma-hydroxybutyrate-induced Fos expression in rat brain: comparison with baclofen. Neurosci. 2009;158(2):441–55. (Epub 2008 Oct 17).

    Article  CAS  Google Scholar 

  91. Zeitzer JM, Buckmaster CL, Parker KL, Hauck CM, Lyons DM, Mignot E. Circadian and homeostatic regulation of hypocretin in a primate model: implications for the consolidation of wakefulness. J Neurosci. 2003;23(8):3555–60.

    CAS  PubMed  Google Scholar 

  92. Huber R, Ghilardi F, Massimini M, Tononi G. Local sleep and learning. Nature 2004;430:78–81.

    Article  CAS  PubMed  Google Scholar 

  93. Lesku A, Vyssotski AL, Martinez-Gonzalez D, Wilzeck C, Rattenborg NC. Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds? Proc Biol Soi. 2011;278(1717):2419–28. (Epub 2011 Jan 5).

    Article  Google Scholar 

  94. Vyazovskiy VV, Olcese U, Hanlon E, Nir Y, Cirelli C, Tononi G. Local sleep in awake rats. Nature. 2011;472(7344):443–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Mignot E. CSF hypocretin-1/orexin-A in narcolepsy: technical aspects and clinical experience in the United States. In: Bassetti CL, Billiard M, Mignot E. Narcolepsy and hypersomnia. New York: Informa Healthcare; 2007. pp. 287–99.

    Google Scholar 

  96. Broughton R. Human consciousness and sleep/waking rhythms: a review and some neuropsychological considerations. J Clin Neuropsychol. 1982;4:193–218.

    Article  CAS  PubMed  Google Scholar 

  97. Mamelak H, Snowden K. The effect of gammahydroxybutyrate on the H-reflex. Neurology. 1983;33(11):1497–500.

    Article  CAS  PubMed  Google Scholar 

  98. Parkes D, Langdon N, Lock C. Narcolepsy and immunity. BMJ. 1986;292(6517):359–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Mignot E, Tafti M, Dement WC, Grumet FC. Narcolepsy and immunity. Adv Neuroimmunol. 1995;5(1):23–37.

    Article  CAS  PubMed  Google Scholar 

  100. Dauvillier Y, Carlander B, Rivier F, Touchon J, Tafti M. Successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset. Ann Neurol. 2004;56:905–8.

    Article  CAS  Google Scholar 

  101. Lavigne GJ. Effect of sleep restriction on pain perception: towards greater attention! Pain. 2010;148(1):6–7. (Epub 2009 Nov 14).

    Article  CAS  PubMed  Google Scholar 

  102. Onen SH, Alloui A, Gross A, Eschallier A, Dubray C. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance threshold in healthy subjects. J Sleep Res. 2001;10(1):35–42.

    Article  CAS  PubMed  Google Scholar 

  103. Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic. Sleep. 2006;29(2):145–51.

    PubMed  Google Scholar 

  104. Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. Adv Neuroimmunol. 1995;5(1):39–56.

    Article  CAS  PubMed  Google Scholar 

  105. Moldofsky H, Lue FA, Eisen J, Keystone E, Gorczynski RM. The relationship of interleukin-1 and immune functions to sleep in humans. Psychosom Med. 1986;48(5):309–18.

    Article  CAS  PubMed  Google Scholar 

  106. Moldofsky H, Lue FA, Davidson JR, Gorczynski R. Effects of sleep deprivation on human immune functions. FASEB. 1989;3(8):1072–7.

    Google Scholar 

  107. Pollmächer T, Mullington J, Korth C, Hinze-Selch D. Influence of host defense activation on sleep in normal. Adv Neuroimmunol. 1995;5(2):155–69.

    Article  PubMed  Google Scholar 

  108. Dickstein JB, Moldofsky H. Sleep, cytokines and immune function. Sleep Med Rev. 1999;3(3):219–28.

    Article  CAS  PubMed  Google Scholar 

  109. Mullington J, Korth C, Hermann DM, Orth A, Galanos C, Holsboer F, Pollmächer T. Dose-dependent effects of endotoxin on human sleep. Am J Physiol Regulatory Integrative Comp Physiol. 2000;278:R947–55.

    CAS  Google Scholar 

  110. Pollmächer T, Schuld A, Kraus T, Haack M, Hinze-Selch D, Mullington J. Experimental immunomodulation, sleep, and sleepiness in humans. Ann N Y Acad Sci. 2000;917:488–99.

    Article  PubMed  Google Scholar 

  111. Mullington JM, Hirze-Selch D, Pollmächer T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions. Ann N Y Acad Med. 2001;933:201–10

    Article  CAS  Google Scholar 

  112. Lorton D, Lubahn CL, Estus C, Millar BA, Carter JL, Wood CA, Bellinger DL. Bidirectional communication between the brain and the immune system: implications for physiological sleep and disorders with disrupted sleep. Neuroimmunomodulation. 2006;13(5/6):357–74. (Epub 2007 Aug 6).

    Article  CAS  PubMed  Google Scholar 

  113. Schuld A, Haack M, Hinze-Salch D, Mullington J, Pollmächer T. Experimental studies on the interaction between sleep and the immune system in humans. Psychother Psychosom Med Psychol. 2005;55(1):29–35.

    Article  PubMed  Google Scholar 

  114. Wrona D. Neural-immune interactions: an integrative view of the bidirectional relationship between the brain and immune systems. J Neuroimmunol. 2006;172(1/2):38–58. (Epub 2006 Jan 10).

    Article  CAS  PubMed  Google Scholar 

  115. Mignot E. Behavioral genetics ’97: genetics of narcolepsy and other sleep disorders. Am J Hum Genet. 1997;60:1289–302.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  116. Broughton R. Narcolepsy (letter to the editor). Can Med Assoc J. 1974;110:1007.

    PubMed Central  CAS  PubMed  Google Scholar 

  117. Mitchell S, Dement WC. Narcolepsy syndromes: antecedent, contiguous and concomitant sleep disordering and deprivation. Psychophysiology. 1968;4:398.

    Google Scholar 

  118. Mullington J, Newman J, Dunham W, Broughton RJ. Phase timing and duration of naps in narcolepsy-cataplexy: preliminary findings. In: Horne J, editor. Sleep ’90. Bochum: Pontenagel; 1990. pp. 158–60.

    Google Scholar 

  119. Castanon-Cervantes O, Wu M, Ehlen JC, Paul K, Gamble KL, Johnson RL, Besing RC, Menaker M, Gewirtz AT, Davidson AJ. Dysregulation of inflammatory responses by chronic circadian disruption. J Immunol. 2010;185(10):5796–805. (Epub 2010 Oct 13).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  120. Billiard M, Laaberki M, Reygrobellet C, Seignalet J, Brissaud L, Besset A. Elevated antibodies to streptococcal antigens in narcoleptic subjects. Sleep Res. 1989;18:201.

    Google Scholar 

  121. Montplaisir J, Poirier G, Lapierre O, Montplaisir S. Streptococcal antibodies in narcolepsy and idiopathic hypersomnia. Sleep Res. 1989;18:271.

    Google Scholar 

  122. Mueller-Eckhardt G, Meier-Ewert K, Schiefer HG. Is there an infectious origin of narcolepsy? Lancet. 1990;17(8686):424.

    Article  Google Scholar 

  123. Longstreth WT Jr, Ton TG, Koepsell TD. Narcolepsy and streptococcal infections. Sleep. 2009;32(12):1548.

    PubMed Central  PubMed  Google Scholar 

  124. Aran A, Lin L, Nevsimalova S, Plazzi G, Chul Hong S, Weiner K, Zeitzer J, Mignot E. Elevated anti-streptococcal antibodies in patients with recent narcolepsy onset. Sleep. 2008;32(8):979–83.

    Google Scholar 

  125. Dauvillier Y, Montplaisir J, Cochen V, Desautels A, Einen M, Lin L, Kawashima M, Barard S, Monaca C, Tiberge M, Filipini D, Tripathy A, Hong Nouven B, Kotagal S, Mignot E. Post-H1N1 narcolepsy-cataplexy. Sleep. 2010;33(11):1428–30.

    Google Scholar 

  126. Fontana A, Gast H, Reith W, Recher M, Birchler T, Bassetti CL. Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent histocompatibility complex class II induced neuronal loss. Brain. 2010;133:1300–11.

    Article  PubMed  Google Scholar 

  127. Bollinger T, Bollinger A, Skrum L, Dimitrov S, Lange T, Solbach W. Sleep-dependent activity of T cells and regulatory T cells. Clin Exp Immunol. 2009;155(2):231–8. (Epub 2008 Nov 24).

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  128. Hallmayer J, Faraco J, Lin L, Hesselson S, Winkelmann J, Kawashima M, Mayer G, Plazzi G, Nevsimalova S, Bourgin P, Hong S-C, Honda Y, Honda M, Högl B, Longstreth WT, Monplaisir J, Kemlink D, Einen M, Chen J, Musone SL, Akana M, Miyagawa T, Duan J, Desautels A, Erhardt C, Hesla PE, Poli F, Frauscher B, Jeong J-H, Lww A-P, Ton TGN, Kvale M, Kolestar L, Dobrovolna M, Nepom GT, Salomon D, Wichmann H-E, Rouleau GA, Gieger C, Levinson DF, Gejman PV, Meitinge T, Young T, Peppard P, Tokunaga K, Kwok P-Y, Rissch N, Mignot E. Narcolepsy is strongly associated with the T-cell receptor alpha locus. Nat Genet. 2009;41(6):708–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  129. Redgrave P, Taha EB, White L, Dean P. Increased food intake following the manipulation of intracerebral dopamine levels with gamma-hydroxybutyrate. Psychopharmacology (Berl). 1982;76(3):273–7.

    Article  CAS  Google Scholar 

  130. Giorgi O, Rubio MC. Decreased 3H-L-quinuclidinyl benzilate binding and muscarine receptor subsensitivity after chronic gamma-butyrolactone treatment. Naunyn Schmiedebergs Arch Pharmacol. 1981;318(1):14–8.

    Article  CAS  PubMed  Google Scholar 

  131. Janowsky DS, el-Yousef MK, Davis JM, Sekerke HJ. A cholinergic-adrenergic hypothesis of mania and depression. Lancet 1972;2(7778):632–5.

    Article  CAS  PubMed  Google Scholar 

  132. Mamelak M. Neurodegeneration, sleep and cerebral energy metabolism: a testable hypothesis. J Geriatr Psychiatry Neurol. 1997;10(1):29–32.

    Article  CAS  PubMed  Google Scholar 

  133. Mamelak M, Hyndman D. Gamma-hydroxybutyrate and oxidative stress. In: Tunnicliff G, Cash C, editors. Gamma-hydroxybutyrate: molecular, functional and clinical aspects. London: Taylor and Francis; 2002. pp. 218–35.

    Google Scholar 

  134. Dauvilliers Y. Narcolepsie. In: Billiard M, Dauvilliers Y, editors. Les Troubles du Sommeil. France: Elsevier Issy-les-Moulineaux; 2012. pp. 201–14.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Neurology, Department of Medicine, University of Ottawa, 1001-20 Driveway, Ottawa, Ontario, Canada

    Roger Broughton MDCM,PhD FRCP(C)

Authors
  1. Roger Broughton MDCM,PhD FRCP(C)
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Roger Broughton MDCM,PhD FRCP(C).

Editor information

Editors and Affiliations

  1. Department of Neurology, New Jersey Neuroscience Institute JFK Medical Center, Edison, New Jersey, USA

    Sudhansu Chokroverty

  2. Department of Neurology, Gui de Chauliac Hospital, Montpellier, France

    Michel Billiard

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Broughton, R. (2015). Gamma-Hydroxybutyrate (Sodium Oxybate): From the Initial Synthesis to the Treatment of Narcolepsy–Cataplexy and Beyond. In: Chokroverty, S., Billiard, M. (eds) Sleep Medicine. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2089-1_63

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2089-1_63

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-2088-4

  • Online ISBN: 978-1-4939-2089-1

  • eBook Packages: MedicineMedicine (R0)

Keywords

Publish with us

Policies and ethics