Download PDF

Neurotherapeutics

, Volume 5, Issue 2, pp 164–180 | Cite as

Current status of symptomatic medical therapy in Parkinson’s disease

Symptomatic Approach

Summary

Symptomatic medical therapies for Parkinson’s disease (PD) have been disease modifying and have led to improvement in daily function, quality of life, and survival. For 40 years, these therapies have been primarily dopaminergic, and currently include the dopamine (DA) precursor levodopa (LD), DA agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors. The roles of all these classes of agents have evolved, with significant changes occurring since the early 2000s. This article reviews the current literature for each of these classes of drugs, with a focus on efficacy and place in the therapeutic scheme. Levodopa is no longer considered to be toxic and, thus, its early use is not only appropriate but recommended. Ergot agonists are no longer in use, and new agents administered in patch form or subcutaneous injections have been approved. The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Selected safety issues are discussed, including the incidence of melanoma in relation to LD; pathological gambling and DA agonists; hepatic toxicity of tolcapone; and the tyramine or so-called cheese reaction with MAO B inhibitors. The article closes with a discussion of future directions and new drugs under development.

Key Words

Parkinson’s disease symptomatic therapy levodopa dopamine agonists COMT inhibitors MAO inhibitors 
Download to read the full article text

References

  1. 1.
    Factor SA. Levodopa. In: Pahwa R, Lyons KE, Handbook of Parkinson’s disease. 4th ed. New York: Informa Healthcare, 2007: 309–334.Google Scholar
  2. 2.
    Hornykiewicz O. L-DOPA: from a biologically inactive amino acid to a successful therapeutic agent. Amino Acids 2002;23: 65–70.PubMedCrossRefGoogle Scholar
  3. 3.
    Hornykiewicz O. Dopamine miracle: from brain homogenate to dopamine replacement. Mov Disord 2002;17: 501–508.PubMedCrossRefGoogle Scholar
  4. 4.
    Agid Y. Levodopa: is toxicity a myth? Neurology 1998;50: 858–863.PubMedGoogle Scholar
  5. 5.
    Agid Y, Ahlskog E, Albanese A, et al. Levodopa in the treatment of Parkinson’s disease: a consensus meeting. Mov Disord 1999; 14: 911–913.PubMedCrossRefGoogle Scholar
  6. 6.
    Cotzias GC, Van Woert M, Shiffer L. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967;276: 374–379.PubMedCrossRefGoogle Scholar
  7. 7.
    Cotzias GC, Papavasiliou PS, Gellene R. Modification of parkinsonism: chronic treatment with L-DOPA. N Engl J Med 1969; 280: 337–345.PubMedCrossRefGoogle Scholar
  8. 8.
    Yahr MD, Duvoisin RC, Schear MJ, Barrett RE, Hoehn MM. Treatment of parkinsonism with levodopa. Arch Neurol 1969;21: 343–354.PubMedGoogle Scholar
  9. 9.
    Kapp W. The history of drugs for the treatment of Parkinson’s disease. J Neural Transm 1992;38: 1–6.Google Scholar
  10. 10.
    Rinne UK, Molsa P. Levodopa with benserazide or carbidopa in Parkinson disease. Neurology 1979;29: 1584–1589.PubMedGoogle Scholar
  11. 11.
    Rinne UK, Birket-Smith E, Dupont E, et al. Levodopa alone and in combination with a peripheral decarboxylase inhibitor benserazide (Madopar) in the treatment of Parkinson’s disease: a controlled clinical trial. J Neurol 1975;211: 1–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Goetz CG, Tanner CM, Shannon KM, et al. Controlled-release carbidopa/levodopa (CR4-Sinemet) in Parkinson’s disease patients with and without motor fluctuations. Neurology 1988;38: 1143–1146.PubMedGoogle Scholar
  13. 13.
    Jankovic J, Schwartz K, Vander Linden C. Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations. Mov Disord 1989;4: 303–309.PubMedCrossRefGoogle Scholar
  14. 14.
    Factor SA, Sanchez-Ramos JR, Weiner WJ, Ingenito AM. Efficacy of Sinemet CR4 in subgroups of patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1989;52: 83–88.PubMedCrossRefGoogle Scholar
  15. 15.
    Factor SA. Parkinson’s Disease: initial treatment with levodopa or dopamine agonists. Curr Treat Options Neurol 2001;3: 479–493.PubMedCrossRefGoogle Scholar
  16. 16.
    Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord 2001;16: 448–458.PubMedCrossRefGoogle Scholar
  17. 17.
    Quinn N, Critchley P, Marsden CD. Young onset Parkinson’s disease. Mov Disord 1987;2: 73–91.PubMedCrossRefGoogle Scholar
  18. 18.
    Van Gerpen JA, Kumar N, Bower JH, Weigand S, Ahlskog JE. Levodopa-associated dyskinesia risk among Parkinson disease patients in Olmsted County, Minnesota, 1976–1990. Arch Neurol 2006;63: 205–209.PubMedCrossRefGoogle Scholar
  19. 19.
    Fahn S, Oakes D, Shoulson I, et al.; Parkinson Study Group. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004;351: 2498–2508.PubMedCrossRefGoogle Scholar
  20. 20.
    Fahn S; Parkinson Study Group. Does levodopa slow or hasten the rate of progression of Parkinson’s disease? J Neurol 2005;252 Suppl 4: iv37-iv42.PubMedCrossRefGoogle Scholar
  21. 21.
    Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE; 056 Study Group. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 2000;342: 1484–1491.PubMedCrossRefGoogle Scholar
  22. 22.
    Holloway RG, Shoulson I, Fahn S, et al.; Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial [Erratum in: Arch Neurol 2005;62:430]. Arch Neurol 2004;61: 1044–1053.PubMedCrossRefGoogle Scholar
  23. 23.
    Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson disease: a randomized controlled trial. JAMA 2000;284: 1931–1938.CrossRefGoogle Scholar
  24. 24.
    Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson’s disease: an evidence-based review: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2002;58: 11–17.PubMedGoogle Scholar
  25. 25.
    Fiala KH, Whetteckey J, Manyam BV. Malignant melanoma and levodopa in Parkinson’s disease: causality or coincidence? Parkinsonism Relat Disord 2003;9: 321–327.PubMedCrossRefGoogle Scholar
  26. 26.
    Olsen JH, Friis S, Frederiksen K, McLaughlin JK, Mellemkjaer L, Moller H. Atypical cancer pattern in patients with Parkinson’s disease. Br J Cancer 2005;92: 201–205.PubMedCrossRefGoogle Scholar
  27. 27.
    Olsen JH, Tangerud K, Wermuth L, Frederiksen K, Friis S. Treatment with levodopa and risk for malignant melanoma. Mov Disord 2007;22: 1252–1257.PubMedCrossRefGoogle Scholar
  28. 28.
    Postuma RB, Lang AE. Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy? Neurology 2004;63: 886–891.PubMedGoogle Scholar
  29. 29.
    Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG. MTHFR 677C-->T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288: 2023–2031.PubMedCrossRefGoogle Scholar
  30. 30.
    Kelly PJ, Rosand J, Kistler JP, et al. Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology 2002;59: 529–536.PubMedGoogle Scholar
  31. 31.
    Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346: 476–483.PubMedCrossRefGoogle Scholar
  32. 32.
    Yasui K, Nakaso K, Kowa H, Takeshima T, Nakashima K. Levodopa-induced hyperhomocysteinaemia in Parkinson’s disease. Acta Neurol Scand 2003;108: 66–67.PubMedCrossRefGoogle Scholar
  33. 33.
    O’Suilleabhain PE, Bottiglieri T, Dewey RB Jr, Sharma S, Diaz-Arrastia R. Modest increase in plasma homocysteine follows levodopa initiation in Parkinson’s disease. Mov Disord 2004;19: 1403–1408.PubMedCrossRefGoogle Scholar
  34. 34.
    Muller T, Kuhn W. Tolcapone decreases plasma levels of Sadenosyl-l-homocysteine and homocysteine in treated Parkinson’s disease patients. Eur J Clin Pharmacol 2006;62: 447–450.PubMedCrossRefGoogle Scholar
  35. 35.
    Valkovic P, Benetin J, Blazicek P, Valkovicova L, Gmitterova K, Kukumberg P. Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients. Parkinsonism Relat Disord 2005;11: 253–256.PubMedCrossRefGoogle Scholar
  36. 36.
    Bostantjopoulou S, Katsarou Z, Frangia T, et al. Endothelial function markers in parkinsonian patients with hyperhomocysteinemia. J Clin Neurosci 2005;12: 669–672.PubMedCrossRefGoogle Scholar
  37. 37.
    Factor SA. Dopamine agonists. Med Clin North Am 1999;83: 415–443, vi-vii.PubMedCrossRefGoogle Scholar
  38. 38.
    Watts RL. The role of dopamine agonists in early Parkinson’s disease. Neurology 1997;49(1 Suppl 1): S34-S48.PubMedGoogle Scholar
  39. 39.
    Calne DB, Teychenne PF, Claveria LE, Eastman R, Greenacre JK, Petrie A. Bromocriptine in parkinsonism. Br Med J 1974;4: 442–444.PubMedCrossRefGoogle Scholar
  40. 40.
    Horvath J, Fross RD, Kleiner-Fisman G, et al. Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. Mov Disord 2004;19: 656–662.PubMedCrossRefGoogle Scholar
  41. 41.
    Antonini A, Poewe W. Fibrotic heart-valve reactions to dopamine-agonist treatment in Parkinson’s disease. Lancet Neurol 2007; 6: 826–829.PubMedCrossRefGoogle Scholar
  42. 42.
    Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med 2007;356: 39–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Piercey MF, Hoffmann WE, Smith MW, Hyslop DK. Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists. Eur J Pharmacol 1996;312: 35–44.PubMedCrossRefGoogle Scholar
  44. 44.
    Mierau J, Schingnitz G. Biochemical and pharmacological studies on pramipexole, a potent and selective dopamine D2 receptor agonist. Eur J Pharmacol 1992;215: 161–170.PubMedCrossRefGoogle Scholar
  45. 45.
    Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry 2004;161: 564–566.PubMedCrossRefGoogle Scholar
  46. 46.
    Lattanzi L, Dell’Osso L, Cassano P, et al. Pramipexole in treatment-resistant depression: a 16-week naturalistic study. Bipolar Disord 2002;4: 307–314.PubMedCrossRefGoogle Scholar
  47. 47.
    Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety 2000; 11: 58–65.PubMedCrossRefGoogle Scholar
  48. 48.
    Tulloch IF. Pharmacologic profile of ropinirole: a nonergoline dopamine agonist. Neurology 1997;49(Suppl 1): S58-S62.PubMedGoogle Scholar
  49. 49.
    Brefel C, Thalamas C, Rayet S, et al. Effect of food on the pharmacokinetics of ropinirole in parkinsonian patients. Br J Clin Pharmacol 1998;45: 412–415.PubMedCrossRefGoogle Scholar
  50. 50.
    LeWitt PA, Lyons KE, Pahwa R. Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology 2007;68: 1262–1267.PubMedCrossRefGoogle Scholar
  51. 51.
    Nisipeanu P, Korczyn AD. Dopamine agonists. In: Factor S, Weiner WJ, editors. Parkinson’s disease: diagnosis and clinical management. 2nd ed. New York: Demos, 2008. p. 515–532.Google Scholar
  52. 52.
    Guldenpfennig WM, Poole KH, Sommerville KW, Boroojerdi B. Safety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease. Clin Neuropharmacol 2005;28: 106–110.PubMedCrossRefGoogle Scholar
  53. 53.
    Parkinson Study Group. A controlled trial of rotigotine monotherapy in early Parkinson’s disease. Arch Neurol 2003;60: 1721–1728.CrossRefGoogle Scholar
  54. 54.
    Schwab RS, Amador LV, Lettvin JY. Apomorphine in Parkinson’s disease. Trans Am Neurol Assoc 1951;56: 251–253.PubMedGoogle Scholar
  55. 55.
    LeWitt PA. Subcutaneously administered apomorphine: pharmacokinetics and metabolism. Neurology 2004;62(Suppl 4): S8-S11.PubMedGoogle Scholar
  56. 56.
    Shannon KM, Bennett JP Jr, Friedman JH; Pramipexole Study Group. Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson’s disease [Erratum in: Neurology 1998;50:838]. Neurology 1997;49: 724–728.PubMedGoogle Scholar
  57. 57.
    Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson disease: a randomized dose-ranging study. JAMA 1997;278: 125–130.CrossRefGoogle Scholar
  58. 58.
    Adler CH, Sethi KD, Hauser RA, et al.; Ropinirole Study Group. Ropinirole for the treatment of early Parkinson’s disease [Erratum in: Neurology 1997;49:1484]. Neurology 1997;49: 393–399.PubMedGoogle Scholar
  59. 59.
    Sethi KD, O’Brien CF, Hammerstad JP, et al.; Ropinirole Study Group. Ropinirole for the treatment of early Parkinson disease: a 12-month experience. Arch Neurol 1998;55: 1211–1216.PubMedCrossRefGoogle Scholar
  60. 60.
    Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease [Erratum in: Neurology 2007;69:617; Neurology 2007;69:2187]. Neurology 2007;68: 272–276.PubMedCrossRefGoogle Scholar
  61. 61.
    Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH. Rotigotine transdermal patch in early Parkinson’s disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord 2007;22: 2398–2404.PubMedCrossRefGoogle Scholar
  62. 62.
    Lieberman A, Ranhosky A, Korts D. Clinical evaluation of pramipexole in advanced Parkinson’s disease: results of a double-blind, placebo-controlled, parallel-group study. Neurology 1997; 49: 162–168.PubMedGoogle Scholar
  63. 63.
    Guttman M; International Pramipexole—Bromocriptine Study Group. Double-blind comparison of pramipexole and bromocriptine treatment with placebo in advanced Parkinson’s disease. Neurology 1997;49: 1060–1065.PubMedGoogle Scholar
  64. 64.
    Lieberman A, Olanow CW, Sethi K, et al.; Ropinirole Study Group. A multicenter trial of ropinirole as adjunct treatment for Parkinson’s disease [Erratum in: Neurology 1999;52:435]. Neurology 1998;51: 1057–1062.PubMedGoogle Scholar
  65. 65.
    Poewe WH, Rascol O, Quinn N, et al.; SP 515 Investigators. Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson’s disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol 2007;6: 513–520.PubMedCrossRefGoogle Scholar
  66. 66.
    Factor SA. Literature review: intermittent subcutaneous apomorphine therapy in Parkinson’s disease. Neurology 2004;62(Suppl 4): S12-S17.PubMedGoogle Scholar
  67. 67.
    Dewey RB Jr, Hutton JT, LeWitt PA, Factor SA. A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events. Arch Neurol 2001;58: 1385–1392.PubMedCrossRefGoogle Scholar
  68. 68.
    Pfeiffer RF, Gutmann L, Hull KL Jr, Bottini PB, Sherry JH. Continued efficacy and safety of subcutaneous apomorphine in patients with advanced Parkinson’s disease. Parkinsonism Relat Disord 2007;13: 93–100.PubMedCrossRefGoogle Scholar
  69. 69.
    Factor SA, McAlarney T, Sanchez-Ramos JR, Weiner WJ. Sleep disorders and sleep effect in Parkinson’s disease. Mov Disord 1990;5: 280–285.PubMedCrossRefGoogle Scholar
  70. 70.
    Frucht S, Rogers JD, Greene PE, Gordon MF, Fahn S. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 1999;52: 1908–1910.PubMedGoogle Scholar
  71. 71.
    Shapira A. Sleep attacks (sleep episodes) with pergolide. Lancet 2000;355: 1332–1333.CrossRefGoogle Scholar
  72. 72.
    Olanow CW, Schapira AH, Roth T. Waking up to sleep episodes in Parkinson’s disease. Mov Disord 2000;15: 212–215.PubMedCrossRefGoogle Scholar
  73. 73.
    Hauser RA, Gauger L, Anderson WM, Zesiewicz TA. Pramipexole-induced somnolence and episodes of daytime sleep. Mov Disord 2000;15: 658–663.PubMedCrossRefGoogle Scholar
  74. 74.
    Tracik F, Ebersbach G. Sudden daytime sleep onset in Parkinson’s disease: polysomnographic recordings. Mov Disord 2001; 16: 500–506.PubMedCrossRefGoogle Scholar
  75. 75.
    Rye DB, Bliwise DL, Dihenia B, Gurecki P. Daytime sleepiness in Parkinson’s disease. J Sleep Res 2000;9: 63–69.PubMedCrossRefGoogle Scholar
  76. 76.
    Meindorfner C, Körner Y, Möller JC, Stiasny-Kolster K, Oertel WH, Krüger HP. Driving in Parkinson’s disease: mobility, accidents, and sudden onset of sleep at the wheel. Mov Disord 2005; 20: 832–842.PubMedCrossRefGoogle Scholar
  77. 77.
    Hobson DE, Lang AE, Martin WRW, et al. Excessive daytime sleepiness and sudden-onset sleep in Parkinson’s disease: a survey of the Canadian Movement Disorders Group. JAMA 2002; 287: 455–463.PubMedCrossRefGoogle Scholar
  78. 78.
    Avorn J, Schneeweiss S, Sudarsky LR, et al. Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol 2005;62: 1242–1248.PubMedCrossRefGoogle Scholar
  79. 79.
    Adler CH, Thorpy MJ. Sleep issues in Parkinson’s disease. Neurology 2005;64(Suppl 3): S12-S20.PubMedGoogle Scholar
  80. 80.
    Galpern WR, Stacy M. Management of impulse control disorders in Parkinson’s disease. Curr Treat Options Neurol 2007;9: 189–197.PubMedCrossRefGoogle Scholar
  81. 81.
    Kurlan R. Disabling repetitive behaviors in Parkinson’s disease. Mov Disord 2004;19: 433–437.PubMedCrossRefGoogle Scholar
  82. 82.
    Friedman JH. Punding on levodopa. Biol Psychiatry 1994;36: 350–351.PubMedCrossRefGoogle Scholar
  83. 83.
    Giovannoni G, O’Sullivan JD, Turner K, Manson AJ, Lees AJ. Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies. J Neurol Neurosurg Psychiatry 2000;68: 423–428.PubMedCrossRefGoogle Scholar
  84. 84.
    Uitti RJ, Tanner CM, Rajput AH, Goetz CG, Klawans HL, Thiessen B. Hypersexuality with antiparkinsonian therapy. Clin Neuropharmacol 1989;12: 375–383.PubMedCrossRefGoogle Scholar
  85. 85.
    Voon V, Hassan K, Zurowski M, et al. Prospective prevalence of pathologic gambling and medication association in Parkinson disease. Neurology 2006;66: 1750–1752.PubMedCrossRefGoogle Scholar
  86. 86.
    Molina JA, Sainz-Artiga MJ, Fraile A, et al. Pathologic gambling in Parkinson’s disease: a behavioral manifestation of pharmacologic treatment? Mov Disord 2000;15: 869–872.PubMedCrossRefGoogle Scholar
  87. 87.
    Driver-Dunckley E, Samanta J, Stacy M. Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurology 2003;61: 422–423.PubMedGoogle Scholar
  88. 88.
    Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE. Pathological gambling caused by drugs used to treat Parkinson disease. Arch Neurol 2005;62: 1377–1381.PubMedCrossRefGoogle Scholar
  89. 89.
    Voon V, Hassan K, Zurowski M, et al. Prevalence of repetitive and reward-seeking behaviors in Parkinson disease. Neurology 2006;67: 1254–1257.PubMedCrossRefGoogle Scholar
  90. 90.
    Weintraub D, Siderowf AD, Potenza MN, et al. Association of dopamine agonist use with impulse control disorders in Parkinson disease. Arch Neurol 2006;63: 969–973.PubMedCrossRefGoogle Scholar
  91. 91.
    Avanzi M, Baratti M, Cabrini S, Uber E, Brighetti G, Bonfa F. Prevalence of pathological gambling in patients with Parkinson’s disease. Mov Disord 2006;21: 2068–2072.PubMedCrossRefGoogle Scholar
  92. 92.
    Morgan JC, Iyer SS, Sethi KD. Impulse control disorders and dopaminergic drugs. Arch Neurol 2006;63: 298–299; author reply 299.PubMedCrossRefGoogle Scholar
  93. 93.
    Lu C, Bharmal A, Suchowersky O. Gambling and Parkinson disease. Arch Neurol 2006;63: 298.PubMedCrossRefGoogle Scholar
  94. 94.
    Voon V, Thomsen T, Miyasaki JM, et al. Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol 2007;64: 212–216.PubMedCrossRefGoogle Scholar
  95. 95.
    Mamikonyan E, Siderowf AD, Duda JE, et al. Long-term follow-up of impulse control disorders in Parkinson’s disease. Mov Disord 2007 Epub ahead of print; doi:10.1002/mds.21770.Google Scholar
  96. 96.
    Gschwandtner U, Aston J, Renaud S, Fuhr P. Pathologic gambling in patients with Parkinson’s disease. Clin Neuropharmacol 2001;24: 170–172.PubMedCrossRefGoogle Scholar
  97. 97.
    Pontone G, Williams JR, Bassett SS, Marsh L. Clinical features associated with impulse control disorders in Parkinson disease. Neurology 2006;67: 1258–1261.PubMedCrossRefGoogle Scholar
  98. 98.
    Imamura A, Uitti RJ, Wszolek ZK. Dopamine agonist therapy for Parkinson disease and pathological gambling. Parkinsonism Relat Disord 2006;12: 506–508.PubMedCrossRefGoogle Scholar
  99. 99.
    Olanow CW; Tasmar Advisory Panel. Tolcapone and hepatotoxic effects. Arch Neurol 2000;57: 263–267.PubMedCrossRefGoogle Scholar
  100. 100.
    Olanow CW, Watkins PB. Tolcapone: an efficacy and safety review. Clin Neuropharmacol 2007;30: 287–294.PubMedCrossRefGoogle Scholar
  101. 101.
    Jorga KM. COMT inhibitors: pharmacokinetic and pharmacodynamic comparisons. Clin Neuropharmacol 1998;21(suppl 1): S9-S16.Google Scholar
  102. 102.
    Olanow CW, Kieburtz K, Stern M, et al. Double-blind, placebo-controlled study of entacapone in levodopa-treated patients with stable Parkinson disease. Arch Neurol 2004;61: 1563–1568.PubMedCrossRefGoogle Scholar
  103. 103.
    Waters CH, Kurth M, Bailey P, et al.; Tolcapone Stable Study Group. Tolcapone in stable Parkinson’s disease: efficacy and safety of long-term treatment. Neurology 1997;49: 665–671.PubMedGoogle Scholar
  104. 104.
    Rajput AH, Martin W, Saint-Hilaire MH, Dorflinger E, Pedder S. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology 1997;49: 1066–1071.PubMedGoogle Scholar
  105. 105.
    Baas H, Beiske AG, Ghika J, et al. Catechol-O-methyltransferase inhibition with tolcapone reduces the “wearing off” phenomenon and levodopa requirements in fluctuating parkinsonian patients. J Neurol Neurosurg Psychiatry 1997;63: 421–428.PubMedCrossRefGoogle Scholar
  106. 106.
    Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients [Erratum in: Ann Neurol 1998;44:292]. Ann Neurol 1997;42: 747–755.CrossRefGoogle Scholar
  107. 107.
    Rascol O, Brooks DJ, Melamed E, et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomised, double-blind, parallel-group trial. Lancet 2005;365: 947–954.PubMedCrossRefGoogle Scholar
  108. 108.
    Factor SA, Molho ES, Feustel PJ, Brown DL, Evans SM. Long-term comparative experience with tolcapone and entacapone in advanced Parkinson’s disease. Clin Neuropharmacol 2001;24: 295–299.PubMedCrossRefGoogle Scholar
  109. 109.
    Entacapone to Tolcapone Switch Study Investigators. Entacapone to tolcapone switch: multicenter double-blind, randomized, active-controlled trial in advanced Parkinson’s disease. Mov Disord 2007;22: 14–19.CrossRefGoogle Scholar
  110. 110.
    Fisher A, Croft-Baker J, Davis M, Purcell P, McLean AJ. Entacapone-induced hepatotoxicity and hepatic dysfunction. Mov Disord 2002;17: 1362–1365; discussion 1397–1400.PubMedCrossRefGoogle Scholar
  111. 111.
    Lew MF, Kricorian G. Results from a 2-year centralized tolcapone liver enzyme monitoring program. Clin Neuropharmacol 2007;30: 281–286.PubMedCrossRefGoogle Scholar
  112. 112.
    Lees AJ, Ratziu V, Tolosa E, Oertel WH. Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson’s disease. J Neurol Neurosurg Psychiatry 2007;78: 944–948.PubMedCrossRefGoogle Scholar
  113. 113.
    Rajput A, Zesiewicz TA, Hauser RA. Monoamine oxidase inhibitors. In: Factor SA, Weiner WJ, editors. Parkinson’s disease: diagnosis and clinical management. 2nd ed. New York: Demos Medical Publishing, 2008. p. 499–514.Google Scholar
  114. 114.
    Westlund KN, Denney RM, Kochersperger LM, Rose RM, Abell CW. Distinct monoamine oxidase A and B populations in primate brain. Science 1985;230: 181–183.PubMedCrossRefGoogle Scholar
  115. 115.
    Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989;321: 1364–1371.CrossRefGoogle Scholar
  116. 116.
    Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1993;328: 176–183.CrossRefGoogle Scholar
  117. 117.
    Golbe LI. Deprenyl as symptomatic therapy in Parkinson’s disease. Clin Neuropharmacol 1988;11: 387–400.PubMedCrossRefGoogle Scholar
  118. 118.
    Golbe LI, Lieberman AN, Muenter MD, et al. Deprenyl in the treatment of symptom fluctuations in advanced Parkinson’s disease. Clin Neuropharmacol 1988;11: 45–55.PubMedCrossRefGoogle Scholar
  119. 119.
    Fowler JS, Volkow ND, Logan J, et al. Slow recovery of human brain MAO B after l-deprenyl (Selegeline) withdrawal. Synapse 1994;18: 86–93.PubMedCrossRefGoogle Scholar
  120. 120.
    Siderowf A, Stern M. Clinical trials with rasagiline: evidence for short-term and long-term effects. Neurology 2006;66(Suppl 4): S80-S88.PubMedGoogle Scholar
  121. 121.
    Seager H. Drug-delivery products and the Zydis fast-dissolving dosage form. J Pharm Pharmacol 1998;50: 375–382.PubMedGoogle Scholar
  122. 122.
    Clarke A, Brewer F, Johnson ES, et al. A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. J Neural Transm 2003;110: 1241–1255.PubMedCrossRefGoogle Scholar
  123. 123.
    Waters CH, Sethi KD, Hauser RA, Molho E, Bertoni JM. Zydis selegiline reduces off time in Parkinson’s disease patients with motor fluctuations: a 3-month, randomized, placebo-controlled study. Mov Disord 2004;19: 426–432.PubMedCrossRefGoogle Scholar
  124. 124.
    Ondo WG, Sethi KD, Kricorian G. Selegiline orally disintegrating tablets in patients with Parkinson disease and “wearing off” symptoms. Clin Neuropharmacol 2007;30: 295–300.PubMedCrossRefGoogle Scholar
  125. 125.
    Thebault JJ, Guillaume M, Levy R. Tolerability, safety, pharmacodynamics, and pharmacokinetics of rasagiline: a potent, selective, and irreversible monoamine oxidase type B inhibitor. Pharmacotherapy 2004;24: 1295–1305.PubMedCrossRefGoogle Scholar
  126. 126.
    Parkinson Study Group. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002;59: 1937–1943.CrossRefGoogle Scholar
  127. 127.
    Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 2004; 61: 561–566.CrossRefGoogle Scholar
  128. 128.
    Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol 2005;62: 241–248.CrossRefGoogle Scholar
  129. 129.
    deMarcaida JA, Schwid SR, White WB, et al. Effects of tyramine administration in Parkinson’s disease patients treated with selective MAO-B inhibitor rasagiline. Mov Disord 2006;21: 1716–1721.PubMedCrossRefGoogle Scholar
  130. 130.
    Clarke A, Johnson ES, Mallard N, et al. A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition. J Neural Transm 2003;110: 1257–1271.PubMedCrossRefGoogle Scholar
  131. 131.
    Bodner RA, Lynch T, Lewis L, Kahn D. Serotonin syndrome. Neurology 1995;45: 219–223.PubMedGoogle Scholar
  132. 132.
    Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705–713.PubMedGoogle Scholar
  133. 133.
    Richard IH, Kurlan R, Tanner C, et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Neurology 1997;48: 1070–1077.PubMedGoogle Scholar
  134. 134.
    Pahwa R, Factor SA, Lyons KE, et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006;66: 983–995.PubMedCrossRefGoogle Scholar
  135. 135.
    Colosimo C, Fabbrini G, Berardelli A. Drug insight: new drugs in development for Parkinson’s disease. Nat Clin Pract Neurol 2006; 2: 600–610.PubMedCrossRefGoogle Scholar
  136. 136.
    Pahwa R, Stacy MA, Factor SA, et al. Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology 2007;68: 1108–1115.PubMedCrossRefGoogle Scholar
  137. 137.
    Bonuccelli U, Del Dotto P. New pharmacologic horizons in the treatment of Parkinson disease. Neurology 2006;67(Suppl 2): S30-S38.PubMedGoogle Scholar
  138. 138.
    Stocchi F, Vacca L, Grassini P, et al. Symptom relief in Parkinson disease by safinamide: biochemical and clinical evidence of efficacy beyond MAO-B inhibition. Neurology 2006;67(Suppl 2): S24-S29.PubMedGoogle Scholar
  139. 139.
    Caccia C, Maj R, Calabresi M, et al. Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology 2006;67(Suppl 2): S18-S23.PubMedGoogle Scholar
  140. 140.
    Hughes AJ, Bishop S, Kleedorfer B, et al. Subcutaneous apomorphine in Parkinson’s disease: response to chronic administration for up to five years. Mov Disord 1993;8: 165–170.PubMedCrossRefGoogle Scholar
  141. 141.
    Nilsson D, Nyholm D, Aquilonius SM. Duodenal levodopa infusion in Parkinson’s disease: long-term experience. Acta Neurol Scand 2001;104: 343–348.PubMedCrossRefGoogle Scholar
  142. 142.
    Bibbiani F, Oh JD, Petzer JP, et al. A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease. Exp Neurol 2003;184: 285–294.PubMedCrossRefGoogle Scholar
  143. 143.
    Hauser RA, Hubble JP, Truong DD. Randomized trial of the adenosine A2A receptor antagonist istradefylline in advanced PD. Neurology 2003;61: 297–303.PubMedGoogle Scholar
  144. 144.
    Savola JM, Hill M, Engstrom M, et al. Fipamezole (JP-1730) is a potent α2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Mov Disord 2003;18: 872–883.PubMedCrossRefGoogle Scholar
  145. 145.
    Adler CH, Singer C, O’Brien C, et al.; Tolcapone Fluctuator Study Group III. Randomized, placebo-controlled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa—carbidopa. Arch Neurol 1998;55: 1089–1095.PubMedCrossRefGoogle Scholar
  146. 146.
    Myllylä VV, Jackson M, Larsen JP, Baas H; Tolcapone International Parkinson’s Disease Study (TIPS) Group I. Efficacy and safety of tolcapone levodopa-treated Parkinson’s disease patients with “wearing-off” phenomenon: a multicentre, double-blind, randomized, placebo-controlled trial. Eur J Neurol 1997;4: 333–341.CrossRefGoogle Scholar
  147. 147.
    Kurth MC, Adler CH, Hilaire MS, et al.; Tolcapone Fluctuator Study Group I. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson’s disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Neurology 1997;48: 81–87.PubMedGoogle Scholar
  148. 148.
    Rinne UK, Larsen JP, Siden A, Worm-Petersen J; Nomecomt Study Group. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Neurology 1998; 51: 1309–1314.PubMedGoogle Scholar
  149. 149.
    Fénelon G, Giménez-Roldán S, Montastruc JL, et al. Efficacy and tolerability of entacapone in patients with Parkinson’s disease treated with levodopa plus a dopamine agonist and experiencing wearing-off motor fluctuations: a randomized, double-blind, multicentre study. J Neural Transm 2003;110: 239–251.PubMedCrossRefGoogle Scholar
  150. 150.
    Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M; Celomen Study Group. Efficacy and safety of entacapone in Parkinson’s disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen Study). Acta Neurol Scand 2002; 105: 245–255.PubMedCrossRefGoogle Scholar

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2008

Authors and Affiliations

  1. 1.Department of NeurologyEmory University School of MedicineAtlanta

Personalised recommendations