Adenosine A2A receptors and Parkinson's disease

Handbook of Experimental Pharmacology

Volumn 193, Issue , 2009, Pages 589-615

  Morelli, Micaela ^a   Carta, Anna R ^a   Jenner, Peter ^b  

^a UNIVERSITY OF CAGLIARI   (Italy)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

6 OHDA; A2A antagonist; Basal ganglia; Clinical trial; Dyskinesia; Motor dysfunction; MPTP; Neuroprotection

Indexed keywords

4 AMINOBUTYRIC ACID; 5 AMINO 2 (2 FURYL) 7 (2 PHENYLETHYL)PYRAZOLO[4,3 E][1,2,4]TRIAZOLO[1,5 C]PYRIMIDINE; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; AMANTADINE; CATECHOL METHYLTRANSFERASE INHIBITOR; DOPAMINE RECEPTOR STIMULATING AGENT; ENTACAPONE; GLUTAMIC ACID; ISTRADEFYLLINE; LEVODOPA; MONOAMINE OXIDASE B INHIBITOR; PRAMIPEXOLE; RASAGILINE; ROPINIROLE; SELEGILINE; ST 1535; TOLCAPONE; UNCLASSIFIED DRUG;

4 AMINOBUTYRIC ACID RELEASE; AREA UNDER THE CURVE; BASAL GANGLION; CENTRAL NERVOUS SYSTEM DISEASE; COGNITION; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENTIATION; DRUG RECEPTOR BINDING; HUMAN; MAXIMUM PLASMA CONCENTRATION; MOTOR ACTIVITY; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; ANIMAL; CHEMISTRY; DRUG ANTAGONISM; GLOBUS PALLIDUS; MUSCLE RIGIDITY; PHYSIOLOGY;

ANIMALS; BASAL GANGLIA; COGNITION; GLOBUS PALLIDUS; HUMANS; MUSCLE RIGIDITY; PARKINSON DISEASE; RECEPTOR, ADENOSINE A2A;

EID: 70349327971     PISSN: 01712004     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-3-540-89615-9_18     Document Type: Review

References (143)

1. Acquas E, Tanda G, Di Chiara G (2002) Differential effects of caffeine on dopamine and acetylcholine transmission in brain areas of drug-naive and caffeine-pretreated rats. Neuropsychopharmacology 27:182-193
2. Agid Y (1991) Parkinson's disease: pathophysiology. Lancet 337:1321-1324
3. Ahlskog JE (2007) I can't get no satisfaction: still no neuroprotection for Parkinson disease. Neurology 69:1476-1477
4. Appollonio I, Grafman J, Clark K, Nichelli P, Zeffiro T, Hallett M (1994) Implicit and explicit memory in patients with Parkinson's disease with and without dementia. Arch Neurol 51:359-367 (Pubitemid 24110519)
5. Ascherio A, Zhang SM, Herńan MA, Kawachi I, Colditz GA, Speizer FE, Willett WC (2001) Prospective study of caffeine consumption and risk of Parkinson's disease in men and women. Ann Neurol 50:56-63
6. Bara-JimenezW, Sherzai A, Dimitrova T, Favit A, Bibbiani F, Gillespie M, Morris MJ, Mouradian MM, Chase TN (2003) Adenosine A(2A) receptor antagonist treatment of Parkinson's disease. Neurology 61:293-296
7. Becker C, Jick SS, Meier CR (2008) Use of antihypertensives and the risk of Parkinson disease. Neurology 70:1438-1444
8. Berg D (2006) Marker for a preclinical diagnosis of Parkinson's disease as a basis for neuroprotection. J Neural Transm Suppl:123-132
9. Bibbiani F, Oh JD, Petzer JP, Castagnoli N Jr, Chen JF, Schwarzschild MA (2003) A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson's disease. Exp Neurol 184:285-294
10. Boraud T, Bezard E, Bioulac B, Gross CE (2001) Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey. Brain 124:546-557
11. Bornebroek M, de Lau LM, Haag MD, Koudstaal PJ, Hofman A, Stricker BH, BretelerMM(2007) Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Neuroepidemiology 28:193-196
12. Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del TK (2006a) Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered. Mov Disord 21:2042-2051
13. Braak H, Muller CM, Rub U, Ackermann H, Bratzke H, de Vos RA, Del TK (2006b) Pathology associated with sporadic Parkinson's disease: where does it end? J Neural Transm Suppl 89-97
14. Braak H, Del TK (2008) Invited article: Nervous system pathology in sporadic Parkinson disease. Neurology 70:1916-1925
15. Brooks DJ, Doder M, Osman S, Luthra SK, Gunn R, Hirani E, Hume S, Kase H, Kilborn J, Martindill S, Mori A (2008) Positron emission tomography analysis of [11C]KW-6002 binding to human and rat adenosine A2A receptors in the brain. Synapse 62:671-681
16. Calabresi P, Picconi B, Parnetti L, Di FM (2006) A convergent model for cognitive dysfunctions in Parkinson's disease: the critical dopamine- acetylcholine synaptic balance. Lancet Neurol 5:974-983
17. Calabresi P, Picconi B, Tozzi A, Di FM (2007) Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci 30:211-219
18. Carta AR, Pinna A, Cauli O, Morelli M (2002) Differential regulation of GAD67, enkephalin and dynorphin mRNAs by chronic-intermittent L-dopa and A2A receptor blockade plus L-dopa in dopamine-denervated rats. Synapse 44:166-174
19. Carta AR, Tabrizi MA, Baraldi PG, Pinna A, Pala P, Morelli M (2003) Blockade of A2A receptors plus L-DOPA after nigrostriatal lesion results in GAD67 mRNA changes different from L-DOPA alone in the rat globus pallidus and substantia nigra reticulata. Exp Neurol 184:679-687
20. Cenci MA, Lee CS, Bjorklund A (1998) L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur J Neurosci 10:2694-2706
21. Chase TN, Bibbiani F, Bara-Jimenez W, Dimitrova T, Oh-Lee JD (2003) Translating A2A antagonist KW6002 from animal models to parkinsonian patients. Neurology 61:S107-11
22. Chaudhuri KR, Yates L, Martinez-Martin P (2005) The non-motor symptom complex of Parkinson's disease: a comprehensive assessment is essential. Curr Neurol Neurosci Rep 5:275-283
23. Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N Jr, Schwarzschild MA (2001) Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease. J Neurosci 21:RC143
24. Chen JF, Sonsalla PK, Pedata F, Melani A, Domenici MR, Popoli P, Geiger J, Lopes LV, de Mendonça A (2007) Adenosine A2A receptors and brain injury: broad spectrum of neuroprotection, multifaceted actions and fine tuning modulation. Prog Neurobiol 83:310-331
25. Coccurello R, Breysse N, Amalric M (2004) Simultaneous blockade of adenosine A2A and metabotropic glutamate mGlu5 receptors increase their efficacy in reversing Parkinsonian deficits in rats. Neuropsychopharmacology 29:1451-1461
26. Correa M, Wisniecki A, Betz A, Dobson DR, O'Neil MF, O'Neil MJ, Salamone JD (2004) The adenosine A2A antagonist KF17837 reverses the locomotor suppression and tremulous jaw movements induced by haloperidol in rats: possible relevance to parkinsonism. Behav Brain Res 148:47-54
27. Cunha RA (2001) Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem Int 38:107-125
28. Dorsey ER, Constantinescu R, Thompson JP, Biglan KM, Holloway RG, Kieburtz K, Marshall FJ, Ravina BM, Schifitto G, Siderowf A, Tanner CM (2007) Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68:384-386
29. Esposito E, Di MV, Benigno A, Pierucci M, Crescimanno G, Di GG (2007) Non-steroidal antiinflammatory drugs in Parkinson's disease. Exp Neurol 205:295-312
30. Fabbrini G, Brotchie JM, Grandas F, NomotoM, Goetz CG (2007) Levodopa-induced dyskinesias. Mov Disord 22:1379-1389
31. Fahn S, Jankovic J (2007) Principles and practice of movement disorders. Elsevier, Philadelphia, pp 1-652
32. Fernandez HH, 6002-US-051 Clinical Investigator Group (2008) The safety and efficacy of istradephylline, an adenosine A2A antagonist, as monotherapy in Parkinson's Disease: results of the KW-6002-US-051 trial. Presented at the 12th International Congress of Parkinson's Disease and Movement Disorders, Chicago. Mov Disord 23(Suppl 1):S87
33. Ferŕe S, Karcz-Kubicha M, Hope BT, Popoli P, Burgueño J, Gutíerrez MA, Casad́o V, Fuxe K, Goldberg SR, Lluis C, Franco R, Ciruela F (2002) Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc Natl Acad Sci USA 99:11940-11945
34. Fink JS, Weaver DR, Rivkees SA, Peterfreund RA, Pollack AE, Adler EM, Reppert SM (1992) Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. Brain Res Mol Brain Res 14:186-195
35. Fredduzzi S, Moratalla R, Monopoli A, Cuellar B, Xu K, Ongini E (2002) Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors. J Neurosci 22:1054-1062
36. Fredholm BB (1995) Purinoceptors in the nervous system. Pharmacol Toxicol 76:228-239
37. Fredholm BB, Abbracchio MP, Burnstock G, Daly JW, Harden TK, Jacobson KA, Leff P,Williams M (1994) Nomenclature and classification of purinoceptors. Pharmacol Rev 46:143-156
38. Fuxe K, Ferŕe S, Canals M, Torvinen M, Terasmaa A, Marcellino D, Goldberg SR, Staines W, Jacobsen KX, Lluis C, Woods AS, Agnati LF, Franco R (2005) Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function. J Mol Neurosci 26:209-220
39. Fuxe K, Marcellino D, Genedani S, Agnati L (2007) Adenosine A(2A) receptors, dopamine D(2) receptors and their interactions in Parkinson's disease. Mov Disord 22:1990-11917
40. Galvan A, Floran B, Erlij D, Aceves J (2001) Intrapallidal dopamine restores motor deficits induced by 6-hydroxydopamine in the rat. J Neural Transm 108:153-166
41. Gao WJ, Goldman-Rakic PS (2003) Selective modulation of excitatory and inhibitory microcircuits by dopamine. Proc Natl Acad Sci USA 100:2836-2841
42. Gasser T (2007) Update on the genetics of Parkinson's disease. Mov Disord 22(Suppl 17):S343-S350
43. Gerfen CR (1992) The neostriatal mosaic: multiple levels of compartmental organization. Trends Neurosci 15:133-139
44. Giḿenez-Llort L, Schiffmann SN, Shmidt T, Canela L, Caḿon L, Wassholm M, Canals M, Terasmaa A, Ferńandez-Teruel A, Tobeña A, Popova E, Ferŕe S, Agnati L, Ciruela F, Martínez E, Scheel-Kruger J, Lluis C, Franco R, Fuxe K, Bader M (2007) Working memory deficits in transgenic rats overexpressing human adenosine A2A receptors in the brain. Neurobiol Learn Mem 87:42-56
45. Grondin R, Bedard PJ, Hadj Tahar A, Gregoire L, Mori A, Kase H (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 52:1673-1677
46. Guridi J, Obeso JA, Rodriguez-Oroz MC, Lozano AA, Manrique M (2008) L-Dopa-induced dyskinesia and stereotactic surgery for Parkinson's disease. Neurosurgery 62:311-323
47. Guttman M, 6002-US-018 Clinical Investigator Group (2006) Efficacy of istradephylline in Parkinson's disease patients treated with levodopa with motor response complications: results of the KW-6002-US-018 study. Presented at the 10th International Congress of Parkinson's Disease and Movement Disorders, Kyoto. Mov Disord 21(Suppl. 15):S585
48. Halldner L, Lozza G, Lindstr̈om K, Fredholm BB (2000) Lack of tolerance to motor stimulant effects of a selective adenosine A(2A) receptor antagonist. Eur J Pharmacol 406:345-354
49. Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A (2006) Genetics of Parkinson's disease and parkinsonism. Ann Neurol 60:389-398
50. Hauber W (1998) Involvement of basal ganglia transmitter systems in movement initiation. Prog Neurobiol 56:507-540
51. Hauber W, Lutz S (1999) Dopamine D1 or D2 receptor blockade in the globus pallidus produces akinesia in the rat. Behav Brain Res 106:143-150
52. HauberW, Neuscheler P, Nagel J, Muller CE (2001) 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 14:1287-1293
53. Hauser RA, Hubble JP, Truong DD (2003) Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology 61:297-303
54. Hauser RA, Schwarzschild MA (2005). Adenosine A2A receptor antagonists for Parkinson's disease: rationale, therapeutic potential and clinical experience. Drugs Aging 22:471-482
55. Hauser R, 6002-US-013 Clinical Investigator Group (2006) Effects of istradephylline (KW-6002) in levodopa treated Parkinson's disease patients with motor response complications: secondary efficacy results of the KW-6002-US-013 study. Presented at the 10th International Congress of Parkinson's Disease and Movement Disorders, Kyoto. Mov Disord 21(Suppl 15):S510
56. Hauser RA, Shulman LM, Trugman JM, Roberts J, Mori A, Ballerini R, Sussman NM(2008) Study of istradefylline in patients with Parkinson's disease on levodopa with motor fluctuations. Mov Disord 23:2177-2185
57. Hillion J, Canals M, Torvinen M, Casado V, Scott R, Terasmaa A, Hansson A, Watson S, Olah ME, Mallol J, Canela EI, Zoli M, Agnati LF, Ibanez CF, Lluis C, Franco R, Ferre S, Fuxe K (2002) Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 277:18091-18097
58. Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen JP, Lees A, Oertel W, Poewe W, Rascol O, Sampaio C (2006a) Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies and the Movement Disorder Society-European Section. Part I: early (uncomplicated) Parkinson's disease. Eur J Neurol 13:1170-1185 (Pubitemid 44581464)
59. Horstink M, Tolosa E, Bonuccelli U, Deuschl G, Friedman A, Kanovsky P, Larsen JP, Lees A, Oertel W, Poewe W, Rascol O, Sampaio C (2006b) Review of the therapeutic management of Parkinson's disease. Report of a joint task force of the European Federation of Neurological Societies (EFNS) and the Movement Disorder Society-European Section (MDS-ES). Part II: late (complicated) Parkinson's disease. Eur J Neurol 13:1186-1202 (Pubitemid 44581465)
60. Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J (2007) Coffee and tea consumption and the risk of Parkinson's disease. Mov Disord 22:2242-2248
61. Hung AY, Schwarzschild MA (2007) Clinical trials for neuroprotection in Parkinson's disease: overcoming angst and futility? Curr Opin Neurol 20:477-483
62. Ikeda K, Kurokawa M, Aoyama S, Kuwana Y (2002) Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson's disease. J Neurochem 80:262-270
63. Jankovic J (2005) Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations. Mov Disord 20(Suppl 11):S11-S16
64. Jankovic J (2006) An update on the treatment of Parkinson's disease. Mt Sinai J Med 73:682-689
65. Jankovic J, Stacy M (2007) Medical management of levodopa-associated motor complications in patients with Parkinson's disease. CNS Drugs 21:677-692
66. Jellinger KA (2002) Recent developments in the pathology of Parkinson's disease. J Neural Transm Suppl 347-376
67. Jenner P (2003) A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD. Neurology 61:S32-S38
68. Jenner P, Olanow CW (2006) The pathogenesis of cell death in Parkinson's disease. Neurology 66:S24-S36
69. Kachroo A, Orlando LR, Grandy DK, Chen JF, Young AB, Schwarzschild MA (2005) Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice. J Neurosci 25:10414-10419
70. Kanda T, Shiozaki S, Shimada J, Suzuki F, Nakamura J (1994) KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity. Eur J Pharmacol 256:263-268
71. Kanda T, Tashiro T, Kuwana Y, Jenner P. (1998a) Adenosine A2A receptors modify motor function in MPTP-treated common marmosets. Neuroreport 9:2857-2860
72. Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner P (1998b) Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43:507-513
73. Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H (2000) 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 162:321-327
74. Kase H, Aoyama S, Ichimura M, Ikeda K, Ishii A, Kanda T, Koga K, Koike N, Kurokawa M, Kuwana Y, Mori A, Nakamura J, Nonaka H, Ochi M, Saki M, Shimada J, Shindou T, Shiozaki S, Suzuki F, Takeda M, Yanagawa K, Richardson PJ, Jenner P, Bedard P, Borrelli E, Hauser RA, Chase TN (2003) Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor selective antagonist KW6002: research and development toward a novel nondopaminergic therapy for Parkinson's disease. Neurology 61:S97-S100
75. Kieburtz K, Ravina B (2007) Why hasn't neuroprotection worked in Parkinson's disease? Nat Clin Pract Neurol 3:240-241 (Pubitemid 46745468)
76. Koga K, Kurokawa M, Ochi M, Nakamura J, Kuwana Y (2000) Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats. Eur J Pharmacol 408:249-255
77. Kulisevsky J, García-Śanchez C, Berthier ML, Barbanoj M, Pascual-Sedano B, Gironell A, Est́evez-Gonźalez A (2000) Chronic effects of dopaminergic replacement on cognitive function in Parkinson's disease: a two-year follow-up study of previously untreated patients. Mov Disord 15(4):613-626
78. Kurokawa M, Koga K, Kase H, Nakamura J, Kuwana Y (1996) Adenosine A2A receptor-mediated modulation of striatal acetylcholine release in vivo. J Neurochem 66:1882-1888
79. Küst BM, Biber K, van Calker D, Gebicke-Haerter PJ (1999) Regulation of K+ channel mRNA expression by stimulation of adenosine A2A-receptors in cultured rat microglia. Glia 25:120-130
80. LeWitt PA (2006) Neuroprotection for Parkinson's disease. J Neural Transm Suppl:113-122
81. LeWitt PA, 6002-US-005/6002-US-006 Clinical Investigator Group (2004) OFF time reduction from adjunctive use of istradephylline (KW-6002) in levodopa-treated patients with advanced Parkinson's disease. Presented at 8th International Congress of Parkinson's Disease and Movement Disorders, Rome. Mov Disord 19(Suppl 9):S222
82. LeWitt PA, Guttman M, Tetrud JW, Tuite PJ, Mori A, Chaikin P, Sussman NM (2008) 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 63:295-302
83. Litvan I, Chesselet MF, Gasser T, Di Monte DA, Parker D Jr, Hagg T, Hardy J, Jenner P, Myers RH, Price D, Hallett M, LangstonWJ, Lang AE, Halliday G, RoccaW, Duyckaerts C, Dickson DW, Ben-Shlomo Y, Goetz CG,Melamed E (2007a) The etiopathogenesis of Parkinson disease and suggestions for future research. Part I. J Neuropathol Exp Neurol 66:251-257 (Pubitemid 46559017)
84. Litvan I, Halliday G, Hallett M, Goetz CG, Rocca W, Duyckaerts C, Ben-Shlomo Y, Dickson DW, Lang AE, Chesselet MF, Langston WJ, Di Monte DA, Gasser T, Hagg T, Hardy J, Jenner P, Melamed E, Myers RH, Parker D Jr, Price DL (2007b) The etiopathogenesis of Parkinson disease and suggestions for future research. Part II. J Neuropathol Exp Neurol 66:329-336 (Pubitemid 46701314)
85. Mally J, Stone TW (1996) Potential role of adenosine antagonist therapy in pathological tremor disorders. Pharmacol Ther 72:243-250
86. Mark MH, 6002-US-007 Clinical Investigator Group (2005) Long-term efficacy of istradephylline in patients with advanced Parkinson's disease. Presented at 9th International Congress of Parkinson's disease and Movement Disorders, New Orleans. Mov Disord 20(Suppl 10):S93
87. McCulloch CC, Kay DM, Factor SA, Samii A, Nutt JG, Higgins DS, Griffith A, Roberts JW, Leis BC, Montimurro JS, Zabetian CP, Payami H (2008) Exploring gene-environment interactions in Parkinson's disease. Hum Genet 123:257-265
88. McGeer PL, McGeer EG (2008) Glial reactions in Parkinson's disease. Mov Disord 23:474-483
89. Mihara T, Mihara K, Yarimizu J, Mitani Y, Matsuda R, Yamamoto H, Aoki S, Akahane A, Iwashita A, Matsuoka N (2007) Pharmacological characterization of a novel, potent adenosine A1 and A2A receptor dual antagonist, 5-[5-amino-3-(4-fluorophenyl)pyrazin- 2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), in models of Parkinson's disease and cognition.J Pharmacol Exp Ther 323:708-719
90. Morelli M (2003) Adenosine A2A antagonists: potential preventive and palliative treatment for Parkinson's disease. Exp Neurol 184:20-23
91. Morelli M, Fenu S, Pinna A, Di Chiara G (1994) Adenosine A2 receptors interact negatively with dopamine D1 and D2 receptors in unilaterally 6-hydroxydopamine-lesioned rats. Eur J Pharmacol 251:21-25
92. Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn AC, Greengard P (2003) Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci USA 100:1322-1327
93. Nishizaki T, Nagai K, Nomura T, Tada H, Kanno T, Tozaki H, Li XX, Kondoh T, Kodama N, Takahashi E, Sakai N, Tanaka K, Saito N (2002) A new neuromodulatory pathway with a glial contribution mediated via A(2a) adenosine receptors. Glia 39:133-147
94. Obeso JA, Rodriguez-Oroz MC, Rodriguez M, Lanciego JL, Artieda J, Gonzalo N, Olanow CW (2000) Pathophysiology of the basal ganglia in Parkinson's disease. Trends Neurosci 23:S8-S19
95. Obeso JA, Rodriguez-Oroz M, Marin C, Alonso F, Zamarbide I, Lanciego JL, Rodriguez-Diaz M (2004) The origin of motor fluctuations in Parkinson's disease: importance of dopaminergic innervation and basal ganglia circuits. Neurology 62:S17-S30
96. Obeso JA, Rodriguez-Oroz MC, Javier Blesa F, Guridi J (2006) The globus pallidus pars externa and Parkinson's disease. Ready for prime time? Exp Neurol 202:1-7
97. Ochi M, Shiozaki S, Kase H (2004) Adenosine A(2A) receptor-mediated modulation of GABA and glutamate release in the output regions of the basal ganglia in a rodent model of Parkinson's disease. Neuroscience 127:223-231
98. O'Neill M, Brown VJ (2006) The effect of the adenosine A(2A) antagonist KW-6002 on motor and motivational processes in the rat. Psychopharmacology 184:46-55
99. Papa SM, Desimone R, Fiorani M, Oldfield EH (1999) Internal globus pallidus discharge is nearly suppressed during levodopa-induced dyskinesias. Ann Neurol 46:732-738
100. Pierri M, Vaudano E, Sager T, Englund U (2005) KW-6002 protects fromMPTP induced dopaminergic toxicity in the mouse. Neuropharmacology 48:517-524
101. Pinna A, di Chiara G,Wardas J, Morelli M (1996) Blockade of A2A adenosine receptors positively modulates turning behaviour and c-Fos expression induced by D1 agonists in dopaminedenervated rats. Eur J Neurosci 8:1176-1181
102. Pinna A, Fenu S, Morelli M (2001) Motor stimulants effects of the adenosine A2A receptor antagonist SCH 58261 do not develop tolerance after repeated treatments in 6-hydroxydopamine lesioned rats. Synapse 39:233-239
103. Pinna A, Corsi C, Carta AR, Valentini V, Pedata F, Morelli M (2002) Modification of adenosine extracellular levels and adenosine A2A receptor mRNA by dopamine denervation. Eur J Pharmacol 446:75-82
104. Pinna A, Pontis S, MorelliM(2007) Adenosine A2A receptor antagonists improve deficits in initiation of movement and sensory motor integration in the unilateral 6-hydroxydopamine rat model of Parkinson's disease. Synapse 61:606-614
105. Pollack AE, Fink JS (1996) Synergistic interaction between an adenosine antagonist and a D1 dopamine agonist on rotational behavior and striatal c-Fos induction in 6-hydroxydopaminelesioned rats. Brain Res 743:124-130
106. Popoli P, Pintor A, Domenici MR, Frank C, Tebano MT, P̀ezzola A, Scarchilli L, Quarta D, Reggio R, Malchiodi-Albedi F, Falchi M, Massotti M (2002) Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum. J Neurosci 22:1967-1975
107. Pourcher E, 6002-US-018 Clinical Investigator Group (2006) Safety and tolerability of istradephylline (KW-6002) in Parkinson's disease with motor response complications: results of the KW-6002-US-018 study. Presented at the 10th International Congress of Parkinson's Disease and Movement Disorders, Kyoto. Mov Disord 21(Suppl 15):S508
108. Powers KM, Kay DM, Factor SA, Zabetian CP, Higgins DS, Samii A, Nutt JG, Griffith A, Leis B, Roberts JW, Martinez ED, Montimurro JS, Checkoway H, Payami H (2008) Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Mov Disord 23:88-95
109. Rao N, Uchimura T, Mori A (2005a) Evaluation of safety, tolerability, and multiple dose pharmacokinetics of istradephylline in healthy subjects. Clin Pharmacol Ther 83(Suppl):PIII-89
110. Rao N, Uchimura T, Mori A (2005b) Evaluation of safety, tolerability, and multiple dose pharmacokinetics of istradephylline in Parkinson's disease patients. Clin Pharmacol Ther 83(Suppl):PIII-88
111. Ritz B, Ascherio A, Checkoway H, Marder KS, Nelson LM, Rocca WA, Ross GW, Strickland D, Van Den Eeden SK, Gorell J (2007) Pooled analysis of tobacco use and risk of Parkinson disease. Arch Neurol 64:990-997
112. Rodrigues RJ, Alfaro TM, Rebola N, Oliveira CR, Cunha RA (2005) Co-localization and functional interaction between adenosine A(2A) and metabotropic group 5 receptors in glutamatergic nerve terminals of the rat striatum. J Neurochem 92:433-441 (Pubitemid 40189447)
113. Rose S, Ramsay Croft N, Jenner P. The novel adenosine A2A antagonist (2007) ST1535 potentiates the effects of a threshold dose of L-dopa in unilaterally 6-OHDA-lesioned rats. Brain Res 1133:110-114
114. Rosin DL, Robeva A, Woodard RL, Guyenet PG, Linden J (1998) Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system. J Comp Neurol 401:163-186
115. Rosin DL, Hettinger BD, Lee A, Linden J (2003) Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology 61:S12-S18
116. Salamone JD, Mayorga AJ, Trevitt JT, Cousins MS, Conlan A, Nawab A (1998) Tremulous jaw movements in rats: a model of parkinsonian tremor. Prog Neurobiol 56:591-611
117. Schapira AH (2008) Progress in neuroprotection in Parkinson's disease. Eur J Neurol 15(Suppl 1):5-13
118. Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57:1062-1067
119. Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferŕe S (2007) Adenosine A2A receptors and basal ganglia physiology. Prog Neurobiol 83:277-292
120. Schwarzschild MA, Agnati L, Fuxe K, Chen JF, Morelli M (2006) Targeting adenosine A2A receptors in Parkinson's disease. Trends Neurosci 29:647-654
121. Shindou T, Richardson PJ, Mori A, Kase H, Ichimura M (2003) Adenosine modulates the striatal GABAergic inputs to the globus pallidus via adenosine A2A receptors in rats. Neurosci Lett 352:167-170
122. Shiozaki S, Ichikawa S, Nakamura J, Kitamura S, Yamada K, Kuwana Y (1999) Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology 147:90-95
123. Shulman LM, 6002-US-013 Clinical Investigator Group (2006) The safety profile of istradephylline (KW-6002) in Parkinson's disease with motor response complications on levodopa/ carbidopa: results of KW-6002-US-013 study. Presented at 10th International Congress of Parkinson's Disease and Movement Disorders, Kyoto. Mov Disord 21(Suppl 15):S488
124. Siderowf A, Stern MB (2006) Preclinical diagnosis of Parkinson's disease: are we there yet? Curr Neurol Neurosci Rep 6:295-301
125. Simola N, Fenu S, Baraldi PG, Tabrizi MA, Morelli M (2004) Blockade of adenosine A2A receptors antagonizes parkinsonian tremor in the rat tacrine model by an action on specific striatal regions. Exp Neurol 189:182-188
126. Simola N, Fenu S, Baraldi PG, Tabrizi MA, Morelli M (2006) Involvement of globus pallidus in the antiparkinsonian effects of adenosine A(2A) receptor antagonists. Exp Neurol 202:255-257
127. Simola N, Fenu S, Baraldi PG, Tabrizi MA, Morelli M (2008) Blockade of globus pallidus adenosine A(2A) receptors displays antiparkinsonian activity in 6-hydroxydopamine-lesioned rats treated with D(1) or D(2) dopamine receptor agonists. Synapse 62:345-351
128. Stacy M, Galbreath A (2008) Optimizing long-term therapy for Parkinson disease: levodopa, dopamine agonists, and treatment-associated dyskinesia. Clin Neuropharmacol 31:51-56
129. Stacy M, 6002-US-005/6002-US-006 Clinical Investigator Group (2004) Istradephylline (KW- 6002) as adjunctive therapy in patients with advanced Parkinson's disease: a positive safety profile with supporting efficacy. Presented at 8th International Congress on Parkinson's Disease and Movement Disorders, Rome. Mov Disord 19(Suppl 9):S215
130. Stacy M, Silver D, Mendis T, Sutton J, Mori A, Chaikin P, Sussman NM (2008) A 12-week, placebo-controlled study (6002-US-006) of istradefylline in Parkinson disease. Neurology 70:2233-2240
131. StameyW, Jankovic J (2008) Impulse control disorders and pathological gambling in patients with Parkinson disease. Neurologist 14:89-99
132. Stocchi F (2003) Prevention and treatment of motor fluctuations. Parkinsonism Relat Disord 9(Suppl 2):S73-S81
133. Stocchi F (2005) Pathological gambling in Parkinson's disease. Lancet Neurol 4:590-592
134. Stocchi F, Olanow CW (2003) Neuroprotection in Parkinson's disease: clinical trials. Ann Neurol 53(Suppl 3):S87-S97
135. Takahashi RN, Pamplona FA, Prediger RD (2008) Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Front Biosci 13:2614-2632
136. Tronci E, Simola N, Borsini F, Schintu N, Frau L, Carminati P, Morelli M (2007) Characterization of the antiparkinsonian effects of the new adenosine A2A receptor antagonist ST1535: acute and subchronic studies in rats. Eur J Pharmacol 566:94-102
137. Trugman JM, 6002-US-013 Clinical Investigator Group (2006) Efficacy of istradephylline (KW- 6002) in levodopa-treated Parkinson's disease patients with motor response complications: primary efficacy results of the KW-6002-US-013 study. Presented at 10th International Congress of Parkinson's Disease and Movement Disorders, Kyoto. Mov Disord 21(Suppl 15):S513
138. Wakabayashi K, Tanji K, Mori F, Takahashi H (2007) The Lewy body in Parkinson's disease: molecules implicated in the formation and degradation of alpha-synuclein aggregates. Neuropathology 27:494-506
139. Wang JH, Ma YY, van den Buuse M (2006) Improved spatial recognition memory in mice lacking adenosine A2A receptors. Exp Neurol 199:438-445
140. Wardas J, Konieczny J, Lorenc-Koci E (2001) SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. Synapse 41:160-171
141. Weintraub D, Comella CL, Horn S (2008a) Parkinson's disease-Part 1: Pathophysiology, symptoms, burden, diagnosis, and assessment. Am J Manag Care 14:S40-S48
142. Weintraub D, Comella CL, Horn S (2008b) Parkinson's disease-Part 2: Treatment of motor symptoms. Am J Manag Care 14:S49-S58
143. Weintraub D, Comella CL, Horn S (2008c) Parkinson's disease-Part 3: Neuropsychiatric symptoms. Am J Manag Care 14:S59-S69