L-DOPA-induced dyskinesia in Parkinson's disease: A drug discovery perspective

Drug Discovery Today

Volumn 15, Issue 19-20, 2010, Pages 867-875

  Buck, Kerstin ^a   Ferger, Boris ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

LEVODOPA;

DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; DYSKINESIA; FALSE POSITIVE RESULT; HUMAN; NONHUMAN; PARKINSON DISEASE; PREDICTION; REVIEW;

ANIMALS; DISEASE MODELS, ANIMAL; DRUG DISCOVERY; DYSKINESIA, DRUG-INDUCED; HUMANS; LEVODOPA; PARKINSON DISEASE;

EID: 77957679563     PISSN: 13596446     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drudis.2010.08.014     Document Type: Review

References (85)

1. Dorsey E.R., et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 2007, 68:384-386.
2. Ahlskog J.E., et al. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov. Disord. 2001, 16:448-458.
3. Pechevis M., et al. Effects of dyskinesias in Parkinson's disease on quality of life and health-related costs: a prospective European study. Eur. J. Neurol. 2005, 12:956-963.
4. Obeso J.A., et al. The evolution and origin of motor complications in Parkinson's disease. Neurology 2000, 55:S13-S20.
5. Rascol O. Medical treatment of levodopa-induced dyskinesias. Ann. Neurol. 2000, 47:S179-S188.
6. Kumar N., et al. Levodopa-dyskinesia incidence by age of Parkinson's disease onset. Mov. Disord. 2005, 20:342-344.
7. Stocchi F., et al. Treatment of levodopa-induced motor complications. Mov. Disord. 2008, 23(Suppl. 3):S599-S612.
8. Metman L.V., et al. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch. Neurol. 1999, 56:1383-1386.
9. Wolf E., et al. Long-term antidyskinetic efficacy of amantadine in Parkinson's disease. Mov. Disord. 2010.
10. Fahn S. How do you treat motor complications in Parkinson's disease: medicine, surgery, or both?. Ann. Neurol. 2008, 64(Suppl. 2):S56-S64.
11. Kleiner-Fisman G., et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov. Disord. 2006, 21(Suppl. 14):S290-S304.
12. Figueiras-Mendez R., et al. Subthalamic nucleus stimulation improves directly levodopa induced dyskinesias in Parkinson's disease. J. Neurol. Neurosurg. Psychiatry 1999, 66:549-550.
13. Bedard P.J., et al. Chronic treatment with l-DOPA, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H]spiperone binding. Brain Res. 1986, 379:294-299.
14. Pearce R.K., et al. Chronic l-DOPA administration induces dyskinesias in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix Jacchus). Mov. Disord. 1995, 10:731-740.
15. Burns R.S., et al. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. U. S. A. 1983, 80:4546-4550.
16. Deutch A.Y., et al. Preferential vulnerability of A8 dopamine neurons in the primate to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurosci. Lett. 1986, 68:51-56.
17. Jenner P., et al. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset. Neurosci. Lett. 1984, 50:85-90.
18. Langston J.W., et al. Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res. 1984, 292:390-394.
19. Fox S.H., et al. Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure. Mov. Disord. 2006, 21:1578-1594.
20. Buck K., et al. Intrastriatal inhibition of aromatic amino acid decarboxylase prevents l-DOPA-induced dyskinesia: a bilateral reverse in vivo microdialysis study in 6-hydroxydopamine lesioned rats. Neurobiol. Dis. 2008, 29:210-220.
21. Cenci M.A., et al. l-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur. J. Neurosci. 1998, 10:2694-2706.
22. Buck K., et al. The selective alpha(1) adrenoceptor antagonist HEAT reduces l-DOPA-induced dyskinesia in a rat model of Parkinson's disease. Synapse 2010, 64:117-126.
23. Dekundy A., et al. Modulation of l-DOPA-induced abnormal involuntary movements by clinically tested compounds: further validation of the rat dyskinesia model. Behav. Brain Res. 2007, 179:76-89.
24. Winkler C., et al. l-DOPA-induced dyskinesia in the intrastriatal 6-hydroxydopamine model of Parkinson's disease: relation to motor and cellular parameters of nigrostriatal function. Neurobiol. Dis. 2002, 10:165-186.
25. Henry B., et al. Characterization of enhanced behavioral responses to l-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. Exp. Neurol. 1998, 151:334-342.
26. Lundblad M., et al. Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease. Eur. J. Neurosci. 2002, 15:120-132.
27. Johnston T.H., et al. A simple rodent assay for the in vivo identification of agents with potential to reduce levodopa-induced dyskinesia in Parkinson's disease. Exp. Neurol. 2005, 191:243-250.
28. Lundblad M., et al. A model of l-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiol. Dis. 2004, 16:110-123.
29. Kovoor A., et al. D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways. J. Neurosci. 2005, 25:2157-2165.
30. Ding Y., et al. Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice, a novel genetic model of Parkinson's disease. Neurobiol. Dis. 2007, 27:11-23.
31. Lin J.H. CSF as a surrogate for assessing CNS exposure: an industrial perspective. Curr. Drug Metab. 2008, 9:46-59.
32. Jenner P. Molecular mechanisms of l-DOPA-induced dyskinesia. Nat. Rev. Neurosci. 2008, 9:665-677.
33. Westin J.E., et al. Persistent changes in striatal gene expression induced by long-term l-DOPA treatment in a rat model of Parkinson's disease. Eur. J. Neurosci. 2001, 14:1171-1176.
34. Westin J.E., et al. Spatiotemporal pattern of striatal ERK1/2 phosphorylation in a rat model of l-DOPA-induced dyskinesia and the role of dopamine D1 receptors. Biol. Psychiatry 2007, 62:800-810.
35. Mela F., et al. Antagonism of metabotropic glutamate receptor type 5 attenuates l-DOPA-induced dyskinesia and its molecular and neurochemical correlates in a rat model of Parkinson's disease. J. Neurochem. 2007, 101:483-497.
36. Rylander D., et al. Pharmacological modulation of glutamate transmission in a rat model of l-DOPA-induced dyskinesia: effects on motor behavior and striatal nuclear signaling. J. Pharmacol. Exp. Ther. 2009, 330:227-235.
37. Jenner P. Preventing and controlling dyskinesia in Parkinson's disease - a view of current knowledge and future opportunities. Mov. Disord. 2008, 23(Suppl. 3):S585-S598.
38. Buck K., et al. The alpha(2) adrenoceptor antagonist idazoxan alleviates l-DOPA-induced dyskinesia by reduction of striatal dopamine levels: an in vivo microdialysis study in 6-hydroxydopamine lesioned rats. J. Neurochem. 2010, 112:444-452.
39. Kornhuber J., et al. Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology 1995, 34:713-721.
40. Blanchet P.J., et al. Amantadine reduces levodopa-induced dyskinesias in parkinsonian monkeys. Mov. Disord. 1998, 13:798-802.
41. Hill M.P., et al. Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson's disease. J. Pharmacol. Exp. Ther. 2004, 310:386-394.
42. Chase T.N., et al. Contribution of dopaminergic and glutamatergic mechanisms to the pathogenesis of motor response complications in Parkinson's disease. Adv. Neurol. 1996, 69:497-501.
43. Loftis J.M., et al. The N-methyl-d-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications. Pharmacol. Ther. 2003, 97:55-85.
44. Nash J.E., et al. The NR2B-selective NMDA receptor antagonist CP-101,606 exacerbates l-DOPA-induced dyskinesia and provides mild potentiation of anti-parkinsonian effects of l-DOPA in the MPTP-lesioned marmoset model of Parkinson's disease. Exp. Neurol. 2004, 188:471-479.
45. Steece-Collier K., et al. Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptors. Exp. Neurol. 2000, 163:239-243.
46. Nutt J.G., et al. Effects of a NR2B selective NMDA glutamate antagonist. CP-101,606, on dyskinesia and parkinsonism. Mov. Disord. 2008, 23:1860-1866.
47. Addy C., et al. Single-dose administration of MK-0657, an NR2B-selective NMDA antagonist, does not result in clinically meaningful improvement in motor function in patients with moderate Parkinson's disease. J. Clin. Pharmacol. 2009, 49:856-864.
48. Gregoire L. Antidyskinetic effect of AFQ056 a novel metabotropic glutamate receptor type 5 (mGluR5) antagonist in MPTP monkeys. Soc. Neurosci. Abstr. 2009, 35:319.
49. Berg D., et al. A randomized, controlled trial evaluating AFQ056 in reducing levodopa-induced dyskinesia in patients with Parkinson's disease. Late Breaking Abstracts of Movements Disorder Society 13th International Congress 2009.
50. Dekundy A., et al. Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease. Brain Res. Bull. 2006, 69:318-326.
51. Levandis G., et al. Systemic administration of an mGluR5 antagonist, but not unilateral subthalamic lesion, counteracts l-DOPA-induced dyskinesias in a rodent model of Parkinson's disease. Neurobiol. Dis. 2008, 29:161-168.
52. Rylander D., et al. A mGluR5 antagonist under clinical development improves l-DOPA-induced dyskinesia in parkinsonian rats and monkeys. Neurobiol. Dis. 2010.
53. Johnston T.H., et al. Reduction of l-DOPA-induced dyskinesia by the selective metabotropic glutamate receptor 5 antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease. J. Pharmacol. Exp. Ther. 2010, 333:865-873.
54. Morin N., et al. Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. Neuropharmacology 2010, 58:981-986.
55. Konradi C., et al. Transcriptome analysis in a rat model of l-DOPA-induced dyskinesia. Neurobiol. Dis. 2004, 17:219-236.
56. Samadi P., et al. mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys. Neurobiol. Aging 2008, 29:1040-1051.
57. Yamamoto N., et al. Metabotropic glutamate mGluR5 receptor blockade opposes abnormal involuntary movements and the increases in glutamic acid decarboxylase mRNA levels induced by l-DOPA in striatal neurons of 6-hydroxydopamine-lesioned rats. Neuroscience 2009, 163:1171-1180.
58. Marin C., et al. Local administration of sarizotan into the subthalamic nucleus attenuates levodopa-induced dyskinesias in 6-OHDA-lesioned rats. Psychopharmacology (Berl.) 2009, 204:241-250.
59. Bibbiani F., et al. Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 2001, 57:1829-1834.
60. Gregoire L., et al. Low doses of sarizotan reduce dyskinesias and maintain antiparkinsonian efficacy of l-DOPA in parkinsonian monkeys. Parkinsonism. Relat. Disord. 2009.
61. Bara-Jimenez W., et al. Effects of serotonin 5-HT1A agonist in advanced Parkinson's disease. Mov. Disord. 2005, 20:932-936.
62. Goetz C.G., et al. Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial. Mov. Disord. 2007, 22:179-186.
63. Iravani M.M., et al. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1a agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with increased motor disability. J. Pharmacol. Exp. Ther. 2006, 319:1225-1234.
64. Carta M., et al. Dopamine released from 5-HT terminals is the cause of l-DOPA-induced dyskinesia in parkinsonian rats. Brain 2007, 130:1819-1833.
65. Munoz A., et al. Serotonin neuron-dependent and -independent reduction of dyskinesia by 5-HT1A and 5-HT1B receptor agonists in the rat Parkinson model. Exp. Neurol. 2009, 219:298-307.
66. Munoz A., et al. Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of l-DOPA-induced dyskinesia. Brain 2008.
67. Kannari K., et al. Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in extracellular dopamine derived from exogenously administered l-DOPA in the striatum with nigrostriatal denervation. J. Neurochem. 2001, 76:1346-1353.
68. Carta M., et al. Involvement of the serotonin system in l-DOPA-induced dyskinesias. Parkinsonism Relat. Disord. 2008, 14(Suppl. 2):S154-S158.
69. Grondin R., et al. Noradrenoceptor antagonism with idazoxan improves l-DOPA-induced dyskinesias in MPTP monkeys. Naunyn Schmiedebergs Arch. Pharmacol. 2000, 361:181-186.
70. Henry B., et al. The alpha2-adrenergic receptor antagonist idazoxan reduces dyskinesia and enhances anti-parkinsonian actions of l-DOPA in the MPTP-lesioned primate model of Parkinson's disease. Mov. Disord. 1999, 14:744-753.
71. Rascol O., et al. Idazoxan, an alpha-2 antagonist, and l-DOPA-induced dyskinesias in patients with Parkinson's disease. Mov. Disord. 2001, 16:708-713.
72. Manson A.J., et al. Idazoxan is ineffective for levodopa-induced dyskinesias in Parkinson's disease. Mov. Disord. 2000, 15:336-337.
73. Savola J.M., et al. Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. Mov. Disord. 2003, 18:872-883.
74. Dimitrova T. Alpha-2 adrenergic antagonist effects in Parkinson's disease. Mov. Disord. 2009, 24:261.
75. Jenner P., et al. Adenosine, adenosine A 2A antagonists, and Parkinson's disease. Parkinsonism Relat. Disord. 2009, 15:406-413.
76. Shiozaki S., et al. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology (Berl.) 1999, 147:90-95.
77. Hauber W., et al. Catalepsy induced by a blockade of dopamine D1 or D2 receptors was reversed by a concomitant blockade of adenosine A(2A) receptors in the caudate-putamen of rats. Eur. J. Neurosci. 2001, 14:1287-1293.
78. Koga K., et al. Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats. Eur. J. Pharmacol. 2000, 408:249-255.
79. Grondin R., et al. Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 1999, 52:1673-1677.
80. Kanda T., et al. Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann. Neurol. 1998, 43:507-513.
81. Kanda T., et al. Combined use of the adenosine A(2A) antagonist KW-6002 with l-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp. Neurol. 2000, 162:321-327.
82. Bara-Jimenez W., et al. Adenosine A(2A) receptor antagonist treatment of Parkinson's disease. Neurology 2003, 61:293-296.
83. Hauser R.A., et al. Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations. Mov. Disord. 2008, 23:2177-2185.
84. Lewitt P.A., et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann. Neurol. 2008, 63:295-302.
85. Stacy M., et al. A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease. Neurology 2008, 70:2233-2240.