Levodopa in Parkinson's disease: Neurotoxicity issue laid to rest?

Drug Safety

Volumn 21, Issue 5, 1999, Pages 339-352

  Murer, M Gustavo ^a   Raisman Vozari, Rita ^b   Gershanik, Oscar ^c  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^b PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^c Facultad de Ciencias Naturales e Instituto M Lillo   (Argentina)

Author keywords

[No Author keywords available]

Indexed keywords

LEVODOPA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; DOPAMINERGIC NERVE CELL; DOPAMINERGIC SYSTEM; DRUG METABOLISM; DRUG OXIDATION; HUMAN; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; INTRAPERITONEAL DRUG ADMINISTRATION; MOUSE; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; RAT;

ANIMALS; ANTIPARKINSON AGENTS; BRAIN; HUMANS; LEVODOPA; PARKINSON DISEASE;

EID: 0032710370     PISSN: 01145916     EISSN: None     Source Type: Journal    
DOI: 10.2165/00002018-199921050-00001     Document Type: Article

References (145)

1. 1. Carlsson A, Lindqvist M, Magnusson T. 3,4-dihydroxy-phenylalanine and 5-hydroxytryptophan as reserpine antagonists [letter]. Nature 1957; 180: 1200
2. 2. Hornykiewicz O, Dopamine (3-hydroxytyramine) and brain function. Pharmacol Rev 1966; 18: 925-64
3. 3. Tolosa E, Marti MJ, Valldeoriola F, et al. History of levodopa and dopamine agonists in Parkinson's disease treatment. Neurology 1998; 50 Suppl. 6: S2-10
4. 4. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967; 276: 374-9
5. 5. Cotzias GC, Papavasiliou PS, Gellene R. Modification of parkinsonism: chronic treatment with L-dopa. N Engl J Med 1969; 280: 337-45
6. 6. Calne DB, Reid JL, Vakil SD, et al. Idiopathic parkinsonism treated with extracerebral decarboxylase inhibitor in combination with levodopa. BMJ 1971; 3: 729-32
7. 7. Yahr MD, Duvoisin RC, Mendoza MR, et al. Modification of L-dopa therapy of parkinsonism by alpha-methyldop hydrazinc [MK486]. Trans Am Neurol Assoc 1971; 96: 55-8
8. 8. Papavasiliou PS Cotzias GC, Düby SE, et al. Levodopa in parkinsonism: potentiation of central effects with a peripheral inhibitor. N Engl J Med 1972; 286: 8-14
9. 9 Fahn S, Calne DB. Considerations in the management of parkinsonism. Neurology 1978; 28: 5-7
10. 10. Lesser RP, Fahn S, Snider SR, et al. Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29: 1253-60
11. 11. Barbeau A. The use of L-Dopa in Parkinson's disease: a 20 year follow-up. Trends Pharmacol Sci 1981; 2: 297-9
12. 12. Markham CH, Diamond SG. Evidence to support early levodopa therapy in Parkinson's disease. Neurology 1981; 31: 125-31
13. 13. Fahn S, Bressman SB. Should levodopa therapy for parkinsonism be started early or late?: evidence against early treatment. Can J Neurol Sci 1984; 11: 200-6
14. 14. Muenter MD. Should levodopa be started early or late? Can J Neurol Sci 1984; 11: 195-9
15. 15. Rajput AH, Stern W, Laverty WH. Chronic low-dose levodopa therapy in Parkinson's disease: an argument for delaying levodopa therapy. Neurology 1984; 34: 991-6
16. 16. Melamed E. Initiation of levodopa therapy in parkinsonian patients should be delayed until the advanced stages of the disease. Arch Neurol 1986; 43: 402-5
17. 17. Cohen G. The pathobiology of Parkinson's disease; biochemical aspects of dopamine neuron senescence. J Neural Transm 1983; Suppl. 19: 89-103
18. 18. Olanow CW. Oxidation reactions in Parkinson's disease. Neurology 1990; 40 Suppl. 3: 32-7
19. 19. Jenner P. Oxidative stress as a cause of Parkinson's disease. Acta Neurol Scand 1991; 84: 6-15
20. 20. Fahn S, Cohen G. The oxidative stress hypothesis in Parkinson's disease: evidence supporting it. Ann Neurol 1992; 32: 804-12
21. 21. Graham DG. Oxidative stress for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 1978; 14: 633-43
22. 22. Graham DG, Tiffany SM, Bell Jr WR, et al. Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward CI300 neuroblastoma cells in vitro. Mol Pharmacol 1978; 14: 644-53
23. 23. Mattammal MB, Haring JH, Chung HD, et al. An endogenous dopaminergic neurotoxin: implications for Parkinson's disease. Neurodegeneration 1995; 4: 271-81
24. 24. Newcomer TA, Rosenberg PA, Aizenman E. TOPA quinone, a kainate-like agonist and excitotoxin, is generated by a catecholaminergic cell line. J Neurosci 1995; 15: 3172-7
25. 25. Naoj M, Maruyama W, Dostert P, et al. N-methyl-(R)salsolinol as a dopaminergic neurotoxin: from an animal model to an early marker of Parkinson's disease. J Neural Transm 1997; 50: 89-105
26. 26. Oreland L. Monoamine oxidase, dopamine, and Parkinson's disease. Acta Neurol Scand 1991; 81 Suppl. 136: 60-5
27. 27. Haavik J, Almas B, Flatmark T. Generation of reactive oxygen species by tyrosine hydroxylase: a possible contribution to the degeneration of dopaminergic neurons? J Neurochem 1997; 68: 328-32
28. 28. Haavik J. L-dopa is a substrate for tyorsine hydroxylase. J Neurochem 1997; 69: 1720-8
29. 29. Hastings TG. Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 1995; 64: 919-24
30. 30. Mattammal MB, Strong R, Lakshmi VM, et al. Prostaglandin H synthetase-mediated metabolism of dopamine: implication for Parkinson's disease. J Neurochem 1995; 64: 1645-54
31. 31. Moldeus P, Nordenskjold G, Bolasfoldi G, et al. Genetic toxicity of dopamine. Mutation Res 1983; 124: 9-24
32. 3H-dopamine: impact of ascorbic acid and glutathione. J Neurochem 1994; 63: 1126-32
33. 33. Li C-L, Werner P, Cohen G. Lipid peroxidation in brain: interactions of L-dopa/dopamine with ascorbate and iron. Neurodegeneration 1995; 4: 147-53
34. 34. Spencer JPE, Jenner A, Butler J, et al. Evaluation of the prooxidant and antioxidant actions of L-dopa and dopamine in vitro: implications for Parkinson's disease. Free Radic Res 1996; 24: 95-105
35. 35. Olney JW, Zorumski CF, Stewart GR, et al. Excitotoxicity of L-DOPA and 6-OH-DOPA: implications for Parkinson's and Huntington's diseases. Exp Neurol 1990; 108: 269-72
36. 36. Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994; 74: 139-62
37. 37. Michel PP, Hefti F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res 1990; 26: 428-35
38. 38. Steece-Collier K, Sladeck, CD, Jr Sladek JR. Chronic levodopa impairs morphological development of grafted embryonic dopamine neurons. Exp Neurol 1990, 110: 201-8
39. 39. Mytilineou C, Han SK, Cohen G. Toxic and protective effects of L-DOPA on mesencephalic cell cultures. J Neurochem 1993; 61: 1470-8
40. 40. Mena MA, Pardo B, Paíno CL, et al. Levodopa toxicity in foetal rat midbrain neurons in culture: modulation by ascorbic acid. Neuroreport 1993; 4: 438-40
41. 41. Pardo B, Mena MA, Casarejos MJ, et al. Toxic effects of L-dopa on mesencephalic cell cultures: protection with antioxidants. Brain Res 1995; 682: 133-43
42. 42. Han S-K, Mytilineou C, Cohen G. L-DOPA up-regulates glutathione and protects mesencephalic cultures against oxidative stress. J Neurochem 1996; 66: 501-10
43. 43. Mena MA, Casarejos MJ, Carazo A, et al. Glia conditioned medium protects fetal rat midbrain neurons in culture from L-dopa toxicity. Neuroreport 1996; 7: 441-5
44. 44. Ling ZD, Pieri S, Carvey PM. Comparison of the neurotoxicity of dopa stereoisomers in cultured dopamine neurons. Clin Neuropharmacol 1996; 4: 360-5
45. 45. Mena MA, Casarejos MJ, Carazo A, et al. Glia protects fetal midbrain dopamine neurons in culture from L-dopa toxicity through multiple mechanisms. J Neural Transm 1997; 104: 317-28
46. 46. Tanaka M, Sotomatsu A, Kanai H, et al. Dopa and dopamine cause cultured neuronal death in the presence of iron. J Neurol Sci 1991; 101: 198-203
47. 47. Mena MA, Pardo B, Casarejos MJ, et al. Neurotoxicity of levodopa on catecholamine-rich human neuroblastoma cells. Mov Disord 1992; 5: 62-73
48. 48. Pardo B, Mena MA, Fahn S, et al. Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line. Mov Disord 1993; 8: 278-84
49. 49. Pardo B, Mena MA, de Yehenes JG. L-DOPA inhibits complex 1 of the electron transport chain in catecholamine-rich human neuroblastoma NB69 cells. J Neurochem 1995; 64: 576-82
50. 50. Basma AN, Morris EJ, Nicklas WJ, et al. L-dopa cytotoxicity to PC12 cells in culture is via its autoxidation. J Neurochem 1995; 64: 825-32
51. 51. Walkinshaw G, Waters CM. Induction of apoptosis in catecholaminergic PC12 cells by L-dopa: implications for the treatment of Pakinson's disease. J Clin Invest 1995; 95: 2458-64
52. 52. Ziv I, Zilkhafalb R, Offen D, et al. Levodopa induces apoptosis in cultured neuronal cells - a possible accelerator of nigrostriatal degeneration in Parkinson's disease. Mov Disord 1997; 12: 17-23
53. 53. Cheng NN, Maeda T, Kume T, et al. Differential neurotoxicity induced by L-dopa and dopamine in cultured striatal neurons. Brain Res 1996; 743: 278-83
54. 54. Alagarsamy S, Phillips M, Papper T, et al. Dopamine neurotoxicity in cortical neurons. Drug Alcohol Depend 1997; 48: 105-11
55. 55. Muenter MD, Tyce GM. L-dopa therapy of Pakinson's disease: plasma L-dopa concentration, therapeutic response and side effects. Mayo Clin Proc 1971; 46: 231-9
56. 56. Olanow CW, Gauger LL, Cedarbaum JM. Temporal relationships between plasma and cerebrospinal fluid pharmacokinetics of levodopa and clinical effect in Parkinson's disease. Ann Neurol 1991; 29: 556-9
57. 57. Benetello P, Furlanut M, Zara G, et al. Plasma levels of levodopa and its metabolites in parkinsonian patients after conventional and controlled-release levodopa-carbidopa associations. Eur Neurol 1993; 33: 69-73
58. 58. Kalit HH, Mytilineou C. Ascorbic acid in mesencephalic cultures: effects on dopaminergic neuron development. J Neurochem 1991; 57: 458-64
59. 59. Tallaksen CM, Bohmer T, Bell H. Concentrations of the water-soluble vitamins thiamin, ascorbic acid, and folic acid in serum and cerebrospinal fluid of healthy individuals. Am J Clin Nutr 1992; 56: 559-64
60. 60. Rebec GV, Pierce C. A vitamin as neuromodulator: ascorbate release into the extracellular fluid of the brain regulates dopaminergic and glutamatergic transmission. Prog Neurobiol 1994; 43: 537-65
61. 61. Riederer P, Sofic E, Rausch W-D, et al. Transition metals, ferrilin, glutathione and ascorbic acid in parkinsonian brains. J Neurochem 1989; 52: 515-20
62. 62. Mena MA, Davila V, Sulzer D. Neurotrophic effects of levodopa in postnatal midbrain dopamine neuron/cortical astrocyte coculture. J Neurochem 1997; 69: 1398-408
63. 3H]mazindol autoradiography. Neuroscience 1991; 43: 95-110
64. 64. Adams CE, Hoffman AF, Hudson JL, et al. Chronic treatment with levodopa and/or selegiline does not affect behavioral recovery induced by fetal ventral mesencephalic grafts in unilaterallyy 6-hydroxydopamine-lesioned rats. Exp Neurol 1994; 130: 261-8
65. 65. Cotzias GC, Miller ST, Nicholson AR, et al. Prolongation of the life-span in mice adapted to large amounts of L-DOPA. Proc Natl Acad Sci U S A 1974; 71: 2466-9
66. 66. Hefti F, Melamed E, Bhawan J, et al. Long-term administration of L-DOPA does not damage dopaminergic neurons in the mouse. Neurology 1981; 31: 1194-5
67. 67. Reches A, Fahn S. Chronic dopa feeding of mice. Neurology 1982; 32: 684-5
68. 68. Perry TL, Yong VW, Foulks JG, et al. Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of L DOPA and carbidopa chronically. J Neurochem 1984; 43: 990-3
69. 69. Quinn NP, Parkes D, Janota I, et al. Case report: preservation of the substantia nigra and locus coeruleus in a patient receiving levodopa (2 g) plus decarboxilase inhibitor over a four-year period. Mov Disord 1986; 1: 65-8
70. 70. Rajput AH, Fenton ME, Birdi S, et al. Is levodopa toxic to human substantia nigra? Mov Disord 1997; 5: 634-8
71. 71. Filloux F, Townsend JJ. Pre-and postsynaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection. Exp Neurol 1993; 119: 79-88
72. 72. Hastings TG, Lewis DA, Zigmond MJ. Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections. Proc Natl Acad Sci U S A 1996; 93: 1956-61
73. 73. Ben-Shachar D, Zuk R, Glinka Y. Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem 1995; 64: 718-23
74. 74. Murer MG, Dziewczapolski G, Menalled L, et al. Chronic levodopa is not toxic for remaining dopaminergic neurons, but instead promotes their recovery, in rats with moderate nigrostriatal lesions. Ann Neurol 1998; 43: 561-75
75. 75 Spencer-Smith T, Jr Parker WD, Jr Bennett JP. L-DOPA in creases nigral production of hydroxyl radicals in vivo: potential L-DOPA toxicity? Neuroreport 1994; 5: 1009-11
76. 76. Przedborski S, Jackson-Lewis V, Muthane U, et al. Chronic L-DOPA administration alters cerebral mitochondrial respiratory chain activity. Ann Neurol 1993; 34: 715-23
77. 77. Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 1990; 54: 823-7
78. 78. Schapira AH, Mann VM, Cooper JM, et al. Anatomic and disease specificity of NADH CoQI reductase (complex 1) deficiency in Parkinson's disease. J Neurochem 1990; 55: 2142-5
79. 79. Perry TL, Yong VW. Idiopathic Parkinson's disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett 1986; 67: 269-74
80. 80. Sofic E, Lange KW, Jellinger K, et al. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci Lett 1992; 142: 128-30
81. 81. Sian J, Dexter DT, Lees AJ, et al. Glutathione-related enzymes in brain in Parkinson's disease. Ann Neurol 1994; 36: 356-61
82. 82. Zigmond MJ, Hastings TG, Abercrombie ED. Neurochemical responses to 6-OHDA and L-DOPA therapy: implications for Parkinson's disease. Ann N Y Acad Sci 1992; 648: 71-86
83. 83. Melamed A, Rosenthal J, Globus M, et al. Suppression of MPTP-induced dopaminergic neurotoxicity in mice by nomifensine and L-dopa. Brain Res 1985; 342: 401-4
84. 84. Ogawa N, Tanaka K, Asanuma M, et al. Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl radicals in vitro. Brain Res 1994; 657: 207-13
85. 85. Naudon B, Bonnet J-J, Costentin J. Acute L-dopa pretreatment potenliates 6-hydroxy-dopamine-induced toxic effects on nigrostriatal dopamine neurons in mice. Brain Res 1995; 701: 151-7
86. 86. Fukuda T, Watabe K, Tanaka J. Effects of bromocriptine and/or L-dopa on neurons in the substantia nigra of MPTP-treated C57BL/6 mice. Brain Res 1996; 728: 274-6
87. 87. Ogawa N, Asanuma M, Kondo Y, et al. Differential effects of chronic L-DOPA treatment on lipid peroxidation in the mouse brain with or without pretreatment with 6-OHDA. Neurosci Lett 1994; 171: 55-8
88. 88. Blunt SB, Jenner P, Marsden CD. Suppressive effect of L-DOPA on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine. Mov Disord 1993; 8: 129-33
89. 89. Dziewczapolski G, Murer MG, Agid Y, et al. Absence of neurotoxicity of chronic L-DOPA in 6-hydroxydopamine-lesioned rats. Neuroreport 1997; 8: 975-9
90. 90. Rioux L, Frohna PA, Joyce JN, et al. The effect of chronic levodopa treatment on pre and postsynaptic markers of dopaminergic function in the striatum of Parkinsonian monkeys. Mov Disord 1997; 12: 148-58
91. 91. Yahr MD, Wolf A, Antunes J-L, et al. Autopsy findings in parkinsonism following treatment with levodopa. Neurology 1972; Suppl. 22: 56-71
92. 92. Jenner P, Dexter DT, Sian J, et al. Oxidative stress as a cause of nigrat cell death in Parkinson's disease and incidental Lewy body disease. Ann Neurol 1992; 32: S82-7
93. 93. Fahn S. Is levodopa toxic? Neurology 1996; 47 Suppl. 3: S184-95
94. 94. Fahn S. Levodopa-induced neurotoxicity. Does it represent a problem for the treatment of Parkinson's disease? CNS Drugs 1997; 8: 376-93
95. 95. Naudon L, Raisman-Vozari R, Edwards RH, et al. Reserpine affects differentially the density of the vesicular monoamine transporter and dihydrotetrabenazine binding sites. Eur J Neurosci 1996; 8: 842-6
96. 96. Burns SR, Pakkenberg H, Kopin IJ. Lack of progression of MPTP-induced parkinsonism during long-term treatment with L-DOPA. Ann Neurol 1985; 18: 117
97. 97. Sweet RD, McDowell FH. Five years' treatment of Parkinson's disease with levodopa: therapeutic results and survival of 100 patients. Ann Intern Med 1975; 83: 456-63
98. 98. Zumstein H, Siegfried J. Mortality among Parkinson patients treated with L-DOPA combined with a decarboxilase inhibitor. Eur Neurol 1976; 14: 321-7
99. 99. Martilla RJ, Rinne UK, Siirtola T, et al. Mortality of patients with Parkinson's disease treated with levodopa. J Neurol 1977; 216: 147-53
100. 100. Joseph C, Chassan JB, Koch ML. Levodopa in Parkinson's disease: a long term appraisal of mortality. Ann Neurol 1978; 3: 116-8
101. 101. Hoehn MMM. Parkinson's disease: progression and mortality. Adv Neurol 1986; 45: 457-61
102. 102. Kurtzke JF, Flaten TP, Murphy FM. Death rates from Parkinson's disease in the Norway reflect increased survival. Neurology 1991; 41: 1665-7
103. 103. Uitti RJ, Ahlskog JE, Maraganore DM, et al. Levodopa therapy and survival in idiopathic Parkinson's disease: Olmsted County project. Neurology 1993; 43: 1918-26
104. 104. Diamond SG, Markham CH, Hoehn MMM, et al. Multi-center study of Parkinson mortality with early vs later dopa treatment. Ann Neurol 1987; 22: 8-12
105. 105. Scigliano G, Musico M, Soliveri P, et al. Mortality associated with early and late levodopa therapy initiation in Parkinson's disease. Neurology 1990; 40: 265-9
106. 106. Rajput AH, Uitti RJ, Offord KP. Timely levodopa (LD) administration prolongs survival in Parkinson's disease. Parkinsonism Relat Disord 1997; 3: 159-65
107. 107. Clarke CE. Does levodopa therapy delay death in Parkinson's disease?: a review of the evidence. Mov Disord 1995; 10: 250-6
108. 108. Ebmeier KP, Calder SA, Crawford JR, et al. Parkinson's disease in Aberdeen: survival after 3.5 years. Acta Neurol Scand 1990; 81: 294-9
109. 109. Louis ED, Marder K, Cote L, et al. Mortality from Parkinson's disease. Arch Neurol 1997; 54: 260-4
110. 110. Ben-Shlomo Y, Churchyard A, Head J, et al. Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and sclegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry. BMJ 1998; 316: 1191-6
111. 111. Przuntek H, Welzel D, Blumner E, et al. Bromocriptine lessens the incidence of mortality in L-Dopa-treated parkinsonian patients: prado-study discontinued. Eur J Clin Pharmacol 1992; 43: 357-63
112. 112. Parkinson Study Group. Mortality in DATATOP: a multicenter trial in early Parkinson's disease. Ann Neurol 1998; 43: 318-25
113. 113. Yahr MD. Long-term levodopa in Parkinson's disease. Lancet 1977; 1: 706-7
114. 114. DeJong GJ, Meervaldt JD, Schmitz PIM. Factors that influence the occurrence of response variations in Parkinson's disease. Ann Neurol 1987; 22: 4-7
115. 115. Roos RAC, Vredevoogd CB, van der Velde EA. Response fluctuations in Parkinson's disease. Neurology 1990; 40: 1344-6
116. 116. Blin J, Bonnet A-M, Agid Y. Does levodopa aggravate Parkinson's disease? Neurology 1988; 38: 1410-6
117. 117. Cedarbaum JM, Gandy SE, McDowel FH. Early initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias or dementia in Parkinson's disease. Neurology 1991; 41: 622-9
118. 118. Caraceni T, Scigliano G, Musicco M. The occurrence of motor fluctuations in parkinsonian patients treated long term with levodopa: role of early treatment and disease progression. Neurology 1991; 41: 380-4
119. 119. Hely MA, Morris JGL, Reid WGL, et al. Age at onset: the major determinant of outcome in Parkinson's disease. Acta Neurol Scand 1995; 92: 455-63
120. 120. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson's disease in DATATOP patients requiring levodopa. Ann Neurol 1996; 39: 37-45
121. 121. Langston JW, Ballard P. Parkinsonism induced by MPTP: implications for treatment and the pathogenesis of Parkinson's disease. Can J Neurol Sci 1984; 11: 160-5
122. 122. Schneider JS. Levodopa-induced dyskinesias in parkinsonian monkeys: relationship to the extent of nigrostriatal damage. Pharmacol Biochem Behav 1989; 34: 193-6
123. 123. Onofrio, C Paci, A Thomas C. Sudden appearance of invalidating dyskinesia-dystonia and off fluctuations after the introduction of levodopa in two dopaminomimetic drug naive patients with stage IV Parkinson's disease. J Neurol Neurosurg Psychiatry 1998; 65: 605-6
124. 124. Koller WC, Weiner WJ, Perlik S, et al. Complications of chronic levodopa therapy: long-term efficacy of drug holiday. Neurology 1981; 31: 473-6
125. 125. Feldman RG, Kaye JA, Lannon MC. Parkinson's disease: follow-up after drug holiday. J Clin Pharmacol 1986, 26: 662-7
126. 126. Rinne UK. Early combination of bromocriptine and levodopa in the treatment of Parkinson's disease: a 5-year follow-up. Neurology 1987; 37: 826-8
127. 127. Mizuno Y, Kondo T, Narabayashi H. Pergolide in the treatment of Parkinson's disease. Neurology 1995; 45 Suppl. 3: S13-21
128. 128. Blanchet PJ, Grondin R, Bedard PJ. Dyskinesia and wearing-off following dopamine D1 agonist treatment in drug-naive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primates. Mov Disord 1996; 11: 91-4
129. 129. Goulet M, Grondin R, Blanchet BJ, et al. Dyskinesias and tolerance induced by chronic treatment with a D1 agonist administered in pulsatile or continuous mode do not correlate with changes of putaminal D1 receptors in drug-naive MPTP monkeys. Brain Res 1996; 719: 129-37
130. 130. Verhagen Metman L, Locatelli ER, Bravi D, et al. Apomorphine responses in Parkinson's disease and the pathogenesis of motor complications. Neurology 1997; 48: 369-72
131. 131. Pearce RK, Banerji T, Jenner P, et al. De novo administration of ropinirole and bromocriptine induces less dyskinesia than L-dopa in the MPTP-treated marmoset. Mov Disord 1998; 13: 234-41
132. 132. Luquin MR, Laguna J, Obeso JA. Selective D2 receptor stimulation induces dyskinesia in parkinsonian monkeys. Ann Neurol 1992; 31: 551-4
133. 133. Fearnley J, Lees AJ. Parkinson's disease: neuropathology. In : Watts RL, Koller WC, editors. Movement disorders: neurological principles and practice. New York: McGraw Hill, 1997: 263-78
134. 134. Bonnet A-M, Loria Y, Saint-Hilaire M-H, et al. Does long-term aggravation of Parkinson's disease result from non-dopaminergic lesions? Neurology 1978; 37: 1539-42
135. 135. Gwinn-Hardy K, Evidente VGH, Waters C, et al. L-dopa slows the progression of familial parkinsonism. Lancet 1999; 353: 1850-1
136. 136. Fahn S. Parkinson's disease, the effect of levodopa and the ELLDOPA trial. Arch Neurol 1999; 56: 529-35
137. 137. Tohgi H, Abe T, Saheki M. Reduced and oxidized forms of glutathione and alpha-tocopherol in the cerebrospinal fluid of parkinsonian patients: comparison between before and after L-dopa treatment. Neurosci Lett 1995; 184: 21-4
138. 138. De Vitry F, Hillion J, Catelon J, et al. Dopamine increases the expression of tyrosine hydroxylase and aromatic amino acid decarboxylase in primary cultures of fetal neurons. Dev Brain Res 1991; 59: 123-31
139. 139. Varela MH, de Mello FG, Linden R. Evidence for an anti-anpoptotic role of dopamine in developing retinal tissue. J Neurochem 1999; 73: 485-92
140. 140. Swarzenski BC, Tang L, Oh YJ, et al. Morphogenic potentials of D2, D3 and D4 dopamine receptors revealed in transfected neuronal cell lines. Proc Natl Acad Sci U S A 1994; 91: 649-53
141. 141. Kostic V, Przedborski S, Flaster E, et al. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease. Neurology 1991; 41: 202-5
142. 142. Gershanik OS. Early-onset parkinsonism. In: Jankovic J, Tolosa E, editors. Parkinson's disease and movement disorders. 2nd ed. Baltimore (MD): Williams and Wilkins, 1993; 235-52
143. 143. Montastruc JL, Rascol O, Senard JM, et al. A randomized controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson's disease: a five year follow up. J Neurol Neurosurg Psychiatry 1994; 57: 1034-8
144. 144. Weiner WJ, Factor SA, Sanchez-Ramos JR, et al. Early combination therapy (bromocriptine and levodopa) does not prevent motor fluctuations in Parkinson's disease. Neurology 1993; 43: 21-7
145. 145. Poewc W. Adjuncts to levodopa therapy. Dopamine agonists. Neurology 1998; 50 Suppl. 6: S23-6