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Neuropharmacology of obstructive sleep apnea and central apnea

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Clinical Pharmacology of Sleep

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Summary and future directions

There has been limited progress in the development of effective pharmacotherapy for sleep apnea. A range of agents has been utilized, but there has been lack of or only modest benefit in the treatment of OSA and CSA using these agents. Anumber of drug therapies are limited as well by significant side effects. The promise of serotonergic drug therapy is yet to be realized, and further developments await the full exploration and understanding of the complex interplay of the various and often counteractive 5-HT receptor subtypes in the CNS and PNS that in concert may affect upper airway patency in sleep and wake states. It is possible that effective OSA drug treatment may necessitate combination drug therapies, for example so that excitatory stimulation of upper airway dilator muscles in sleep is combined with pharmacological inhibitory actions on constrictor/relaxant mechanisms.

Given the lack of acceptance of CPAP in mild to moderate cases of OSA, better understanding of the neuropharmacology of OSA and potential pharmacotherapies is imperative.

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References

  1. Villaneuva AT, Buchanan PR, Yee BJ, Grunstein RR (2005) Ethnicity and obstructive sleep apnoea. Sleep Medicine Reviews; doi: 10.1016/j.smrv.2005.04.005

    Google Scholar 

  2. Young T, Peppard PE, Gottlieb DJ (2002) Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 165: 1217–1239

    Article  PubMed  Google Scholar 

  3. Gastaut H, Tassinari CA, Duron B (1965) Polygraphic study of diurnal and nocturnal (hypnic and respiratory) episodal manifestations of Pickwick syndrome. Rev Neurol (Paris) 112: 568–579

    CAS  Google Scholar 

  4. Hla KM, Young TB, Bidwell T, Palta M, Skatrud JB, Dempsey J (1994) Sleep apnea and hypertension. A population-based study. Ann Intern Med 120: 382–388

    PubMed  CAS  Google Scholar 

  5. Gami AS, Howard DE, Olson EJ, Somers VK (2005) Day-night pattern of sudden death in obstructive sleep apnea. N Engl J Med 352: 1206–1214

    Article  PubMed  CAS  Google Scholar 

  6. Marin JM, Carrizo SJ, Vicente E, Agusti AGN (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. The Lancet 365(9464):1046–1053

    Google Scholar 

  7. Masa JF, Rubio M, Findley LJ (2000) Habitually sleepy drivers have a high frequency of automobile crashes associated with respiratory disorders during sleep. Am J Respir Crit Care Med 162: 1407–1412

    PubMed  CAS  Google Scholar 

  8. Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V (2005) Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 353;19:2034–2041

    Article  PubMed  CAS  Google Scholar 

  9. Young T, M Palta, J. Dempsey, J. Skatrud, S. Weber, and S. Badr. 1993. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 328: 1230–1235

    Article  PubMed  CAS  Google Scholar 

  10. Gould GA, Whyte KF, Rhind GB, Airlie MA, Catterall JR, Shapiro CM, Douglas NJ (1988) The sleep hypopnea syndrome. Am Rev Respir Dis 137: 895–898

    PubMed  CAS  Google Scholar 

  11. Strollo PJ Jr., Rogers RM (1996) Obstructive sleep apnea. N Engl J Med 334: 99–104

    Article  PubMed  Google Scholar 

  12. Malhotra A, White DP (2002) Obstructive sleep apnoea. The Lancet 360(9328): 237

    Article  Google Scholar 

  13. Louis ED (2003) Chapter 14: Cranial Nerves XI (Spinal Accessory) and XII (Hypoglossal). In: CG Goetz (ed.): Textbook of Clinical Neurology, 2nd edition. Saunders, Philadelphia, 227; an imprint of Elsevier

    Google Scholar 

  14. Grunstein RR (2005) Chapter 89-Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea-Hypopnea Syndrome, Principles and Practice of Sleep Medicine, 4th edition ed. Elsevier Saunders, Philadelphia

    Google Scholar 

  15. Sher AE (2002) Upper airway surgery for obstructive sleep apnea. Sleep Med Rev 6: 195–212

    Article  PubMed  Google Scholar 

  16. Schmidt-Nowara W, Lowe A, Wiegand L, Cartwright R, Perez-Guerra F, Menn S (1995) Oral appliances for the treatment of snoring and obstructive sleep apnea: a review. Sleep 18: 501–510

    PubMed  CAS  Google Scholar 

  17. Cistulli PA, Gotsopoulos H, Marklund M, Lowe AA (2004) Treatment of snoring and obstructive sleep apnea with mandibular repositioning appliances. Sleep Medicine Reviews 8: 443

    PubMed  Google Scholar 

  18. Mezzanotte WS, Tangel DJ, White DP (1992) Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest 89: 1571–1579

    PubMed  CAS  Google Scholar 

  19. Horner RL (2000) Impact of brainstem sleep mechanisms on pharyngeal motor control. Respir Physiol 119: 113–121

    Article  PubMed  CAS  Google Scholar 

  20. Berger AJ (2000) Determinants of respiratory motoneuron output. Respir Physiol 122:259–269

    Article  PubMed  CAS  Google Scholar 

  21. Soja PJ, Finch DM, Chase MH (1987) Effect of inhibitory amino acid antagonists on masseteric reflex suppression during active sleep. Exp Neurol 96: 178–193

    Article  PubMed  CAS  Google Scholar 

  22. Veasey SC (2003) Serotonin agonists and antagonists in obstructive sleep apnea: therapeutic potential. Am J Respir Med 2: 21–29

    PubMed  CAS  Google Scholar 

  23. Kurasawa I, Toda K, Nakamura Y (1990) Non-reciprocal facilitation of trigeminal motoneurons innervating jaw-closing and jaw-opening muscles induced by iontophoretic application of serotonin in the guinea pig. Brain Res 515: 126–134

    Article  PubMed  CAS  Google Scholar 

  24. Berger AJ, Bayliss DA, Viana F (1992) Modulation of neonatal rat hypoglossal motoneuron excitability by serotonin. Neurosci Lett 143: 164–168

    Article  PubMed  CAS  Google Scholar 

  25. Kubin L, Tojima H, Davies RO, Pack AI (1992) Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat. Neurosci Lett 139: 243–248

    Article  PubMed  CAS  Google Scholar 

  26. Bayliss DA, Viana F, Talley EM, Berger AJ (1997) Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms. Respir Physiol 110: 139–150

    Article  PubMed  CAS  Google Scholar 

  27. Ribeiro-do-Valle LE, Metzler CW, Jacobs BL (1991) Facilitation of masseter EMG and masseteric (jaw-closure) reflex by serotonin in behaving cats. Brain Res 550: 197–204

    Article  PubMed  CAS  Google Scholar 

  28. Douse MA, White DP (1996) Serotonergic effects on hypoglossal neural activity and reflex responses. Brain Res 726: 213–222

    Article  PubMed  CAS  Google Scholar 

  29. Veasey SC, Fornal CA, Metzler CW, Jacobs BL (1995) Response of serotonergic caudal raphe neurons in relation to specific motor activities in freely moving cats. J Neurosci 15(7 Pt 2): 5346–5359

    PubMed  CAS  Google Scholar 

  30. Kubin L, Davies RO, Pack AI (1998) Control of Upper Airway Motoneurons During REM Sleep. News Physiol Sci 13: 91–97

    PubMed  Google Scholar 

  31. Woch G, Davies RO, Pack AI, Kubin L (1996) Behaviour of raphe cells projecting to the dorsomedial medulla during carbachol-induced atonia in the cat. J Physiol 490 (Pt 3): 745–758

    PubMed  CAS  Google Scholar 

  32. Jacobs BL, Azmitia EC (1992) Structure and function of the brain serotonin system. Physiol Rev 72: 165–229

    PubMed  CAS  Google Scholar 

  33. Jelev A, Sood S, Liu H, Nolan P, Horner RL (2001) Microdialysis perfusion of 5-HT into hypoglossal motor nucleus differentially modulates genioglossus activity across natural sleep-wake states in rats. J Physiol 532 (Pt 2): 467–481

    Article  PubMed  CAS  Google Scholar 

  34. Veasey SC, Panckeri KA, Hoffman EA, Pack AI, Hendricks JC (1996) The effects of serotonin antagonists in an animal model of sleep-disordered breathing. Am J Respir Crit Care Med 153: 776–786

    PubMed  CAS  Google Scholar 

  35. Veasey SC, Fenik P, Panckeri K, Pack AI, Hendricks JC (1999) The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog. Am J Respir Crit Care Med 160(5 Pt 1): 1659–1667

    PubMed  CAS  Google Scholar 

  36. Horner RL (2001) The neuropharmarcology of upper airway motor control in the awake and sleep states: inplications for obstructive sleep apnea. Resp Res 2: 286–294

    Article  CAS  Google Scholar 

  37. Aghajanian GK, Sanders-Bush E (2002) Chapter 2. Serotonin, Neuropsychopharmacology: The Fifth Generation of Progress. American College of Neuropsychopharmacology. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  38. Zhan G, Shaheen F, Mackiewicz M, Fenik P, Veasey SC (2002) Single cell laser dissection with molecular beacon polymerase chain reaction identifies 2A as the predominant serotonin receptor subtype in hypoglossal motoneurons. Neuroscience 113: 145–154

    Article  PubMed  CAS  Google Scholar 

  39. Okabe S, Kubin L (1996) Role of 5HT1 receptors in the control of hypoglossal motoneurons in vivo. Sleep 19(10 Suppl): S150–S153

    PubMed  CAS  Google Scholar 

  40. Fenik P, Ogawa H, Veasey SC (2001) Hypoglossal nerve response to 5-HT3 drugs injected into the XII nucleus and vena cava in the rat. Sleep 24: 871–878

    PubMed  CAS  Google Scholar 

  41. Lalley PM, Bischoff AM, Schwarzacher SW, Richter DW (1995) 5-HT2 receptor-controlled modulation of medullary respiratory neurones in the cat. J Physiol 487 (Pt 3): 653–661

    PubMed  CAS  Google Scholar 

  42. Monteau R, Pasquale ED, Hilaire G (1994) Further evidence that various 5-HT receptor subtypes modulate central respiratory activity: in vitro studies with SR 46349B. Eur J Pharm 259: 71–74

    Article  CAS  Google Scholar 

  43. Sutton PM (1981) The interaction between reflex apnoea and bradycardia produced by injecting 5-HT into the nodose ganglion of the cat. Pflugers Arch 389: 181–187

    Article  PubMed  CAS  Google Scholar 

  44. Carley DW, Radulovacki M (1999) Role of peripheral serotonin in the regulation of central sleep apneas in rats. Chest 115: 1397–1401

    Article  PubMed  CAS  Google Scholar 

  45. Radulovacki M, Trbovic SM, Carley DW (1998) Serotonin 5-HT3-receptor antagonist GR 38032F suppresses sleep apneas in rats. Sleep 21: 131–136

    PubMed  CAS  Google Scholar 

  46. Veasey SC, Chachkes J, Fenik P, Hendricks JC (2001) The effects of ondansetron on sleep-disordered breathing in the English bulldog. Sleep 24: 155–160

    PubMed  CAS  Google Scholar 

  47. Veasey SC, Zhan G, Fenik P, Pratico D (2004) Long-Term Intermittent Hypoxia: Reduced Excitatory Hypoglossal Nerve Output. Am J Respir Crit Care Med 170:665–672

    Article  PubMed  Google Scholar 

  48. Schmidt HS (1983) L-tryptophan in the treatment of impaired respiration in sleep. Bull Eur Physiopathol Respir 19: 625–629

    PubMed  CAS  Google Scholar 

  49. Sack KE, Criswell LA (1992) Eosinophilic-myalgia syndrome: the aftermath. South Med J 85: 878–882

    PubMed  CAS  Google Scholar 

  50. Mendelson WB, Martin JV, Rapoport DM (1990) Effects of buspirone on sleep and respiration. Am Rev Respir Dis 141: 1527–1530

    PubMed  CAS  Google Scholar 

  51. Ogasa T, Ray AD, Michlin CP, Farkas GA, Grant BJB, Magalang UJ (2004) Systemic Administration of Serotonin 2A/2C Agonist Improves Upper Airway Stability in Zucker Rats. Am J Respir Crit Care Med 170: 804–810

    Article  PubMed  Google Scholar 

  52. Hanzel DA, Proia NG, Hudgel DW (1991) Response of obstructive sleep apnea to fluoxetine and protriptyline. Chest 100: 416–421

    PubMed  CAS  Google Scholar 

  53. Kraiczi H, Hedner J, Dahlof P, Ejnell H, Carlson J (1999) Effect of serotonin uptake inhibition on breathing during sleep and daytime symptoms in obstructive sleep apnea. Sleep 22: 61–67

    PubMed  CAS  Google Scholar 

  54. Salazar-Grueso EF, Rosenberg RS, Roos RP (1988) Sleep apnea in olivopontocerebellar degeneration: treatment with trazodone. Ann Neurol 23: 399–401

    Article  PubMed  CAS  Google Scholar 

  55. Berry RB, Koch GL, Hayward LF (2005) Low-dose mirtazapine increases genioglossus activity in the anesthetized rat. Sleep 28: 78–84

    PubMed  Google Scholar 

  56. Carley DW, Olopade C, Seink S, Radulovacki M (2003) Serotonin Antagonist Improves Obstructive Sleep Apnea. Sleep Medicine 4S1: S1–S56, 025

    Google Scholar 

  57. Stradling J, Smith D, Radulovacki M, Carley D (2003) Effect of ondansetron on moderate obstructive sleep apnoea, a single night, placebo-controlled trial. J Sleep Res 12: 169–170

    Article  PubMed  Google Scholar 

  58. Carley DW, Paviovic S, Janelidze M, Radulovacki M (2002) Functional role for cannabinoids in respiratory stability during sleep. Sleep 25: 391–398

    PubMed  Google Scholar 

  59. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S (2005) Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. The Lancet 365(9468): 1389–1397

    Article  CAS  Google Scholar 

  60. Mills PJ, Dimsdale JE (2004) Sleep apnea: a model for studying cytokines, sleep, and sleep disruption. Brain Behav Immun 18: 298–303

    Article  PubMed  CAS  Google Scholar 

  61. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP (1997) Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 82: 1313–1316

    Article  PubMed  CAS  Google Scholar 

  62. Vgontzas AN, Papanicolaou DA, Bixler EO, Hopper K, Lotsikas A Lin HM, Kales A, Chrousos GP (2000) Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 85: 1151–1158

    Article  PubMed  CAS  Google Scholar 

  63. Entzian P, Linnemann K, Schlaak M, Zabel P (1996) Obstructive sleep apnea syndrome and circadian rhythms of hormones and cytokines. Am J Respir Crit Care Med 153: 1080–1086

    PubMed  CAS  Google Scholar 

  64. Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, Hirano T, Adachi M (2003) Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation 107: 1129–1134

    Article  PubMed  CAS  Google Scholar 

  65. Vgontzas AN, Zoumakis E, Lin HM, Bixler EO, Trakada G, Chrousos GP (2004) Marked Decrease in Sleepiness in Patients with Sleep Apnea by Etanercept, a Tumor Necrosis Factor-alpha Antagonist. J Clin Endocrinol Metab 89: 4409–4413

    Article  PubMed  CAS  Google Scholar 

  66. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785): 458–462

    Article  PubMed  CAS  Google Scholar 

  67. Nelesen RA, Yu H, Ziegler MG, Mills PJ, Clausen JL, Dimsdale JE (2001) Continuous positive airway pressure normalizes cardiac autonomic and hemodynamic responses to a laboratory stressor in apneic patients. Chest 119: 1092–1101

    Article  PubMed  CAS  Google Scholar 

  68. Brownell LG, West P, Sweatman P, Acres JC, Kryger MH (1982) Protriptyline in obstructive sleep apnea: a double-blind trial. N Engl J Med 307: 1037–1042

    Article  PubMed  CAS  Google Scholar 

  69. Nykamp K, Rosenthal L, Folkerts M, Roehrs T, Guido P, Roth T (1998) The effects of REM sleep deprivation on the level of sleepiness/alertness. Sleep 21: 609–614

    PubMed  CAS  Google Scholar 

  70. Smith I, Lasserson T, Wright J (2002) Drug treatments for obstructive sleep apnoea. Cochrane Database Syst Rev 2: CD003002

    Google Scholar 

  71. Grunstein RR, Hedner J, L Grote (2001) Treatment options for sleep apnoea. Drugs 61: 237–251

    Article  PubMed  CAS  Google Scholar 

  72. Cook WR, Benich JJ, Wooten SA (1989) Indices of severity of obstructive sleep apnea syndrome do not change during medroxyprogesterone acetate therapy. Chest 96: 262–266

    PubMed  CAS  Google Scholar 

  73. Wesstrom J, Ulfberg J, Nilsson S (2005) Sleep apnea and hormone replacement therapy: a pilot study and a literature review. Acta Obstet Gynecol Scand 84: 54–57

    Article  PubMed  Google Scholar 

  74. Shahar E, Redline S, Young T, Boland LL, Baldwin CM, Nieto FJ, O’Connor GT, Rapoport DM, Robbins JA (2003) Hormone Replacement Therapy and Sleep-disordered Breathing. Am J Respir Crit Care Med 167: 1186–1192

    Article  PubMed  Google Scholar 

  75. Cistulli PA, Barnes DJ, Grunstein RR, Sullivan CE (1994) Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women. Thorax 49: 699–702

    Article  PubMed  CAS  Google Scholar 

  76. Saaresranta T, Polo-Kantola P, Rauhala E, Polo O (2001) Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep. Eur Respir J 18: 989–995

    Article  PubMed  CAS  Google Scholar 

  77. Weichler U, Herres-Mayer B, Mayer J, Weber K, Hoffmann R, Peter JH (1991) Influence of antihypertensive drug therapy on sleep pattern and sleep apnea activity. Cardiology 78: 124–130

    Article  PubMed  CAS  Google Scholar 

  78. Kantola I, Rauhala E, Erkinjuntti M, Mansury L (1991) Sleep disturbances in hypertension: a double-blind study between isradipine and metoprolol. J Cardiovasc Pharmacol 18,Suppl 3: S41–S45

    PubMed  Google Scholar 

  79. Heitmann J, Grote L, Knaack L, Kohler U, Hinder M, Peter JH (1998) Cardiovascular effects of mibefradil in hypertensive patients with obstructive sleep apnea. Eur J Clin Pharmacol 54: 691–696

    Article  PubMed  CAS  Google Scholar 

  80. Issa FG (1992) Effect of clonidine in obstructive sleep apnea. Am Rev Respir Dis 145(2 Pt 1): 435–439

    PubMed  CAS  Google Scholar 

  81. Hedner J, Kraiczi H, Peker Y, Murphy P (2003) Reduction of Sleep-disordered Breathing after Physostigmine. Am J Respir Crit Care Med 168: 1246–1251

    Article  PubMed  Google Scholar 

  82. Kirkness JP, Madronio M, Stavrinou R, Wheatley JR, Amis TC (2003) Relationship between surface tension of upper airway lining liquid and upper airway collapsibility during sleep in obstructive sleep apnea hypopnea syndrome. J Appl Physiol 95: 1761–1766

    PubMed  Google Scholar 

  83. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J (2000) Longitudinal study of moderate weight change and sleep-disordered beathing. JAMA 284: 3015–3021

    Article  PubMed  CAS  Google Scholar 

  84. Smith PL, Gold AR, Meyers DA, Haponik EF, Bleecker ER (1985) Weight loss in mildly to moderately obese patients with obstructive sleep apnea. Ann Intern Med 103 (6 Pt 1): 850–855

    PubMed  CAS  Google Scholar 

  85. Schwartz AR, Gold AR, Schubert N, Stryzak A, Wise RA, Permutt S, Smith PL (1991) Effect of weight loss on upper airway collapsibility in obstructive sleep apnea. Am Rev Resp Dis 144 (3 Pt 1): 494–498

    PubMed  CAS  Google Scholar 

  86. Yee BJ, Banerjee D, Wong K, Vedam H, Ward J, Phillips C (2004) Effect of sibutramine-assisted weight loss on obstructive sleep apnea in men. J Sleep Res 13: S72

    Google Scholar 

  87. Schwab RJ (1998) Upper airway imaging. Clin Chest Med 19: 33–54

    Article  PubMed  CAS  Google Scholar 

  88. Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens R, Maislin G, Pack AI (2003) Identification of Upper Airway Anatomic Risk Factors for Obstructive Sleep Apnea with Volumetric Magnetic Resonance Imaging. Am J Respir Crit Care Med 168: 522–530

    Article  PubMed  Google Scholar 

  89. Li Z, Maglione M, Tu W, Mojica W, Arterburn D, Shugarman LR, Hilton L, Suttorp M, Solomon V, Shekelle PG, Morton SC (2005) Meta-Analysis: Pharmacologic Treatment of Obesity. Ann Intern Med 142: 532–546

    PubMed  CAS  Google Scholar 

  90. Maggard MA, Shugarman LR, Suttorp M, Maglione M, Sugarman HJ, Livingston EH, Nguyen NT, Li Z, Mojica WA, Hilton L, Rhodes S, Morton SC, Shekelle PG (2005) Meta-Analysis: Surgical Treatment of Obesity. Ann Intern Med 142: 547–559

    PubMed  Google Scholar 

  91. Snow V, Barry P, Fitterman N, Qaseem A, K Weiss; for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (2005) Pharmacologic and Surgical Management of Obesity in Primary Care: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med 142: 525–531

    PubMed  Google Scholar 

  92. Orzack MH, Friedman LM, Marby DW (1990)Weight changes on fluoxetine as a function of baseline weight in depressed outpatients. Psychopharmacol Bull 26: 327–330

    PubMed  CAS  Google Scholar 

  93. Ferguson JM, Feighner JP (1987) Fluoxetine-induced weight loss in overweight non-depressed humans. Int J Obes 11,Suppl 3: 163–170

    PubMed  Google Scholar 

  94. O’Kane M, Wiles PG, Wales JK (1994) Fluoxetine in the treatment of obese type 2 diabetic patients. Diabet Med 11: 105–110

    Article  PubMed  CAS  Google Scholar 

  95. Breum L, Bjerre U, Bak JF, Jacobsen S, Astrup A (1995) Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. Metabolism 44: 1570–1576

    Article  PubMed  CAS  Google Scholar 

  96. Arnold LM, McElroy SL, Hudson JI, Welge JA, Bennett AJ, Keck PE (2002) A placebo-controlled, randomized trial of fluoxetine in the treatment of binge-eating disorder. J Clin Psychiatry 63: 1028–1033

    PubMed  CAS  Google Scholar 

  97. Settle EC, Stahl SM, Batey SR, Johnston JA, Ascher JA (1999) Safety profile of sustained-release bupropion in depression: results of three clinical trials. Clin Ther 21 454–463

    Article  PubMed  CAS  Google Scholar 

  98. Holm KJ, Spencer CM (2000) Bupropion: a review of its use in the management of smoking cessation. Drugs 59: 1007–1024

    Article  PubMed  CAS  Google Scholar 

  99. Gadde KM, Parker CB, Maner LG, Wagner HR 2nd, Logue EJ, Drezner MK, Krishnan KR (2001) Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women. Obes Res 9: 544–551

    PubMed  CAS  Google Scholar 

  100. Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O’Neil PM (2002) Bupropion SR enhances weight loss: a 48-week double-blind, placebo-controlled trial. Obes Res 10: 633–641

    Article  PubMed  CAS  Google Scholar 

  101. Szkudlarek J, Elsborg L (1993) Treatment of severe obesity with a highly selective serotonin re-uptake inhibitor as a supplement to a low calorie diet. Int J Obes Relat Metab Disord 17: 681–683

    PubMed  CAS  Google Scholar 

  102. McElroy SL, Hudson JI, Malhotra S, Welge JA, Nelson EB, Keck PE Jr. (2003) Citalopram in the treatment of binge-eating disorder: a placebo-controlled trial. J Clin Psychiatry 64: 807–813

    Article  PubMed  CAS  Google Scholar 

  103. Malhotra S, King KH, Welge JA, Brusman-Lovins L, McElroy SL (2002) Venlafaxine treatment of binge-eating disorder associated with obesity: a series of 35 patients. J Clin Psychiatry 63: 802–806

    PubMed  CAS  Google Scholar 

  104. Roy Chengappa KN, Levine J, Rathore D, Parepally H, Atzert R (2001) Long-term effects of topiramate on bipolar mood instability, weight change and glycemic control: a case-series. Eur Psychiatry 16: 186–190

    Article  PubMed  CAS  Google Scholar 

  105. Richard D, Ferland J, Lalonde J, Samson P, Deshaies Y (2000) Influence of topiramate in the regulation of energy balance. Nutrition 16: 961–966

    Article  PubMed  CAS  Google Scholar 

  106. Picard F, Deshaies Y, Lalonde J, Samson P, Richard D (2000) Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats. Obes Res 8: 656–663

    PubMed  CAS  Google Scholar 

  107. Shapira NA, Goldsmith TD, McElroy SL (2000) Treatment of binge-eating disorder with topiramate: a clinical case series. J Clin Psychiatry 61: 368–372

    PubMed  CAS  Google Scholar 

  108. Appolinario JC, Coutinho W, Fontenelle L (2001) Topiramate for binge-eating disorder. Am J Psychiatry 158: 967–968

    PubMed  CAS  Google Scholar 

  109. Bray GA, Hollander P, Klein S, Kushner R, Levy B, Fitchet M, Perry BH (2003) A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 11: 722–733

    PubMed  CAS  Google Scholar 

  110. Wilding J, Van Gaal L, Rissanen A, Vercruysse F, Fitchet M (2004) A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes Relat Metab Disord 28: 1399–1410

    Article  PubMed  CAS  Google Scholar 

  111. Oommen KJ, Mathews S (1999) Zonisamide: a new antiepileptic drug. Clin Neuropharmacol 22: 192–200

    PubMed  CAS  Google Scholar 

  112. Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR (2003) Zonisamide for weight loss in obese adults: a randomized controlled trial. Jama 289: 1820–1825

    Article  PubMed  CAS  Google Scholar 

  113. Rolls BJ, Shide DJ, Thorwart ML, Ulbrecht JS (1998) Sibutramine reduces food intake in non-dieting women with obesity. Obes Res 6: 1–11

    PubMed  CAS  Google Scholar 

  114. Stock MJ (1997) Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Metab Disord 21,Suppl 1: S25–S29

    PubMed  CAS  Google Scholar 

  115. Hansen DL, Toubro S, Stock MJ, Macdonald IA, Astrup A (1998) Thermogenic effects of sibutramine in humans. Am J Clin Nutr 68: 1180–1186

    PubMed  CAS  Google Scholar 

  116. Lean ME (2001) How does sibutramine work? Int J Obes Relat Metab Disord 25,Suppl 4: S8–S11

    PubMed  CAS  Google Scholar 

  117. Lean ME (1997) Sibutramine-a review of clinical efficacy. Int J Obes Relat Metab Disord 21,Suppl 1: S30–S36; discussion 37–39

    PubMed  CAS  Google Scholar 

  118. Wirth A, Krause J (2001) Long-term weight loss with sibutramine: a randomized controlled trial. Jama 286: 1331–1339

    Article  PubMed  CAS  Google Scholar 

  119. Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E (1999) Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med 106: 179–184

    Article  PubMed  CAS  Google Scholar 

  120. Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB (1999) Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. Jama 281: 235–242

    Article  PubMed  CAS  Google Scholar 

  121. Hauptman J, Lucas C, Boldrin MN, Collins H, Segal KR (2000) Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med 9: 160–167

    Article  PubMed  CAS  Google Scholar 

  122. Hill JO, Hauptman J, Anderson JW, Fujioka K, O’Neil PM, Smith DK, Zavoral JH, Aronne LJ (1999) Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Am J Clin Nutr 69: 1108–1116

    PubMed  CAS  Google Scholar 

  123. Tonstad S, Pometta D, Erkelens DW, Ose L, Moccetti T, Schouten JA, Golay A, Reitsma J, Del Bufalo A, Pasotti E et al. (1994) The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia. Eur J Clin Pharmacol 46: 405–410

    Article  PubMed  CAS  Google Scholar 

  124. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, Lubina JA, Patane J, Self B, Hunt P, McCamish M (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. Jama 282: 1568–1575

    Article  PubMed  CAS  Google Scholar 

  125. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O’Rahilly S (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110: 1093–1103

    Article  PubMed  CAS  Google Scholar 

  126. Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaminergic role in stimulant-induced wakefulness. J Neurosci 21: 1787–1794

    PubMed  CAS  Google Scholar 

  127. Ishizuka T, Sakamoto Y, Sakurai T, Yamatodani A (2003) Modafinil increases histamine release in the anterior hypothalamus of rats. Neurosci Lett 339: 143–146

    Article  PubMed  CAS  Google Scholar 

  128. Ferraro L, Antonelli T, O’Connor WT, Tanganelli S, Rambert FA, Fuxe K (1997) Modafinil: an antinarcoleptic drug with a different neurochemical profile to d-amphetamine and dopamine uptake blockers. Biol Psychiatry 42: 1181–1183

    Article  PubMed  CAS  Google Scholar 

  129. Gallopin T, Luppi PH, Rambert FA, Frydman A, Fort P (2004) Effect of the wake-promoting agent modafinil on sleep-promoting neurons from the ventrolateral preoptic nucleus: an in vitro pharmacologic study. Sleep 27: 19–25

    PubMed  Google Scholar 

  130. Pack AI, Black JE, Schwartz JR, Matheson JK (2001) Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med 164: 1675–1681

    PubMed  CAS  Google Scholar 

  131. Schwartz JRL, Hirshkowitz M, Erman MK, Schmidt-Nowara W (2003) Modafinil as Adjunct Therapy for Daytime Sleepiness in Obstructive Sleep Apnea: A 12-Week, Open-Label Study. Chest 124: 2192–2199

    Article  PubMed  CAS  Google Scholar 

  132. Dinges DF, Weaver TE (2003) Effects of modafinil on sustained attention performance and quality of life in OSA patients with residual sleepiness while being treated with nCPAP. Sleep Med 4: 393–402

    Article  PubMed  Google Scholar 

  133. Kingshott RN, Vennelle M, Coleman EL, Engleman HM, Mackay TW, Douglas NJ (2001) Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 163: 918–923

    PubMed  CAS  Google Scholar 

  134. Black JE, Hirshkowitz M (2005) Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep 28: 464–471

    PubMed  Google Scholar 

  135. Hedner J, Grunstein R, Ericksson B, Ejnell H (1996) A double-blind, randomized trial of sabeluzole, a putative glutamate antagonist, in obstructive sleep apnea. Sleep 19: 287–289

    PubMed  CAS  Google Scholar 

  136. Torvaldsson S, Grote L, Peker Y, Basun H, Hedner JAN (2005) A randomized placebo-controlled trial of an NMDA receptor antagonist in sleep-disordered breathing. J Sleep Res 14: 149–155

    Article  PubMed  Google Scholar 

  137. Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD (1999) Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med 160: 1101–1106

    PubMed  CAS  Google Scholar 

  138. Javaheri S, Parker TJ, Liming JD, Corbett WS, Nishiyama H, Wexler L, Roselle GA (1998) Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation 97: 2154–2159

    PubMed  CAS  Google Scholar 

  139. Bradley TD, Floras JS (2003) Sleep apnea and heart failure: Part II: central sleep apnea. Circulation 107: 1822–1826

    Article  PubMed  Google Scholar 

  140. Franklin KA, Eriksson P, Sahlin C, Lundgren R (1997) Reversal of central sleep apnea with oxygen. Chest 111: 163–169

    PubMed  CAS  Google Scholar 

  141. Staniforth AD, Kinnear WJ, Starling R, Hetmanski DJ, Cowley AJ (1998) Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration. Eur Heart J 19: 922–928

    Article  PubMed  CAS  Google Scholar 

  142. Naughton MT, Benard DC, Rutherford R, Bradley TD (1994) Effect of continuous positive airway pressure on central sleep apnea and nocturnal PCO2 in heart failure. Am J Respir Crit Care Med 150 (6 Pt 1): 1598–1604

    PubMed  CAS  Google Scholar 

  143. Naughton MT, Rahman MA, Hara K, Floras JS, Bradley TD (1995) Effect of continuous positive airway pressure on intrathoracic and left ventricular transmural pressures in patients with congestive heart failure. Circulation 91: 1725–1731

    PubMed  CAS  Google Scholar 

  144. Bradley TD, Holloway RM, McLaughlin PR, Ross BL, Walters J, Liu PP (1992) Cardiac output response to continuous positive airway pressure in congestive heart failure. Am Rev Respir Dis 145 (2 Pt 1): 377–382

    PubMed  CAS  Google Scholar 

  145. Sin DD, Logan AG, Fitzgerald FS, Liu PP, Bradley TD (2000) Effects of continuous positive airway pressure on cardiovascular outcomes in heart failure patients with and without Cheyne-Stokes respiration. Circulation 102: 61–66

    PubMed  CAS  Google Scholar 

  146. Bradley TD, Logan AG, Kinoff RJ, Sériès F, Morrison D, Ferguson K, Belenkie I, Pfeifer M, Fleetham J, Hanly P et al.; for the CAN Investigators (2005) Continous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 353;19: 2025–2033

    Article  PubMed  CAS  Google Scholar 

  147. Whyte KF, Gould GA, Airlie MA, Shapiro CM, Douglas NJ (1988) Role of protriptyline and acetazolamide in the sleep apnea/hypopnea syndrome. Sleep 11: 463–472

    PubMed  CAS  Google Scholar 

  148. Javaheri S, Parker TJ, Wexler L, Liming JD, Lindower P, Roselle GA (1996) Effect of theophylline on sleep-disordered breathing in heart failure. N Engl J Med 335: 562–567

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Sleep and Circadian Research Group, Woolcock Institute of Medical Research, Australia

    Peter R. Buchanan & Ronald R. Grunstein

  2. Sleep Investigation Unit, Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia

    Peter R. Buchanan & Ronald R. Grunstein

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  1. Peter R. Buchanan
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  2. Ronald R. Grunstein
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  1. Comprehensive Center for Sleep Medicine, Department of Pulmonary, Critical Care, and Sleep Medicine, Mount Sinai School of Medicine, 1176, 5th Avenue, New York, NY, 10029, USA

    S. R. Pandi-Perumal

  2. Pharmacology and Therapeutics, 2833/602 Zudanez Street, Montevideo, 11300, Uruguay

    Jaime M. Monti

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Buchanan, P.R., Grunstein, R.R. (2006). Neuropharmacology of obstructive sleep apnea and central apnea. In: Pandi-Perumal, S.R., Monti, J.M. (eds) Clinical Pharmacology of Sleep. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7440-3_3

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