Blocking striatal adenosine A2A receptors: A new strategy for basal ganglia disorders

Recent Patents on CNS Drug Discovery

Volumn 2, Issue 1, 2007, Pages 1-21

  Müller, Christa E ^a   Ferré, Sergi ^b  

^a UNIVERSITY OF BONN   (Germany)

^b NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

Author keywords

A2A receptor; Adenine analog; Adenine derivative; Adenosine; Adenosine receptor; Antagonist; Istradefylline; Parkinson's disease; Pharmacophore model; Xanthines

Indexed keywords

2 AMINOPURINE; 2 AMINOURACIL DERIVATIVE; 3,7 DIMETHYL 1 PROPARGYLXANTHINE; 4 AMINOURACIL DERIVATIVE; 8 ETHOXY 9 ETHYLADENINE; ADENINE DERIVATIVE; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; ANR 94; BENZOTHIAZOLE DERIVATIVE; CAFFEINE; CARBIDOPA; DOPAMINE RECEPTOR STIMULATING AGENT; FUROPYRIMIDINE DERIVATIVE; HETEROCYCLIC COMPOUND; ISTRADEFYLLINE; LEVODOPA; MSX 2; MSX 3; OXAZOLO[5,4 D]PYRIMIDINE DERIVATIVE; PLACEBO; PYRAZOLO[2,3 D]PYRIMIDINE DERIVATIVE; PYRAZOLO[3,4 D]PYRIMIDINE DERIVATIVE; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINOXALINE DERIVATIVE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; URACIL DERIVATIVE; VER 6497; XANTHINE DERIVATIVE;

ADJUVANT THERAPY; CATALEPSY; CLINICAL TRIAL; CORPUS STRIATUM; DEGENERATIVE DISEASE; DEPRESSION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG INDICATION; DRUG INDUSTRY; DRUG METABOLISM; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DYSKINESIA; EXTRAPYRAMIDAL SYNDROME; GABAERGIC SYSTEM; HUMAN; HUNTINGTON CHOREA; MONOTHERAPY; MOTOR DYSFUNCTION; NEUROMODULATION; NONHUMAN; PARKINSON DISEASE; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; RECEPTOR AFFINITY; RECEPTOR BLOCKING; RECEPTOR INTRINSIC ACTIVITY; RESTLESS LEGS SYNDROME; REVIEW;

EID: 34248355605     PISSN: 15748898     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488907779561772     Document Type: Review

References (190)

1. Gerfen CR. Basal Ganglia. In: Paxinos G Ed., The Rat Nervous System. Amsterdam. Elsevier Academic Press. 2004; 445-508.
2. Ferré S, Fredholm BB, Morelli M, Popoli P, Fuxe K. Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 1997; 20: 482-87.
3. Ferré S, Borycz J, Goldberg SR, et al. Role of adenosine in the control of homosynaptic plasticity in striatal excitatory synapses. J Integr Neurosci. 2005; 4: 445-64.
4. Tepper JM, Bolam JP. Functional diversity and specificity of neostriatal interneurons. Curr Opin Neurobiol 2004; 14: 685-92.
5. Parent A, Hazrati LN. Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop. Brain Res Rev 1995; 20: 91-127.
6. Penney JB Jr., Young AB. Speculations on the function of basal ganglia disorders. Ann Rev Neurosci 1983; 6: 73-94.
7. Agnati LF, Ferré S, Lluis C, Franco R, Fuxe K. Molecular mechanisms and therapeutical implications of intramembrane receptor /receptor interactions among heptahelical receptors with examples from the striatopallidal GABA neurons. Pharmacol Rev 2003; 55: 509-50.
8. McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P. Failure of the ubiquitin-proteasome system in Parkinson's disease. Nat Rev Neurosci 2001; 2: 589-94.
9. Obeso JA, Rodriguez-Oroz MC, Rodriguez M, et al. Pathophysiology of the basal ganglia in Parkinson's disease. Trends Neurosci 2000; 23: S8-19.
10. Obeso JA, Rodriguez-Oroz MC, Rodriguez M, et al. Pathophysiologic basis of surgery for Parkinson's disease. Neurology 2000; 55: S7-12.
11. Victor M, Ropper AH. Degenerative diseases of the nervous system. In: Adams and Victor's Principles of Neurology. New York, McGraw-Hill. 2001: 1106-74.
12. Gusella JF, Wexler NS, Conneally PM, et al. A polymorphic DNA marker genetically linked to Huntington's disease. Nature 1983; 306: 234-38.
13. Kremer B, Goldberg P, Andrew SE, et al. A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994; 330: 1401-1406.
14. Reiner A, Albin RL, Anderson KD, et al. Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci USA 1988; 85: 5733-37.
15. Heinsen H, Strik M, Bauer M, et al. Cortical and striatal neurone number in Huntington's disease. Acta Neuropathol 1994; 88: 320-33.
16. Rosin DL, Hettinger BD, Lee A, Linden J. Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology 2003; 61: S12-S18.
17. Ciruela F, Casado V, Rodrigues RJ, et al. Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 2006; 26: 2080-87.
18. Greengard P, Allen PB, Nairn AC. Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade. Neuron 1999; 23: 435-47.
19. 1 receptors stimulates cyclic AMP-dependent phosphorylation of DARPP-32 in distinct populations of striatal projection neurons. Neuroscience 1998; 84: 223-28.
20. Lindskog M, Svenningsson P, Pozzi L, et al. Involvement of DARPP-32 phosphorylation in the stimulant action of caffeine. Nature 2002; 418: 774-78.
21. Borsook D, Hyman SE. Proenkephalin gene regulation in the neuroendocrine hypothalamus: a model of gene regulation in the CNS. Am J Physiol 1995; 269: E393-408.
22. Herdegen T, Leah JD. Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 1998; 28: 370-490.
23. Håkansson K, Galdi S, Hendrick J, et al. Regulation of phosphorylation of the GluR1 AMPA receptor by dopamine D2 receptors. J Neurochem 2006; 96: 482-88.
24. Lee HK, Takamiya K, Han JS, et al. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 2003; 112: 631-43.
25. Ferré S, von Euler G, Johansson B, Fredholm BB, Fuxe K. Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc Natl Acad Sci USA 1991; 88: 7238-41.
26. Ferré S, O'Connor WT, Foxe K, Ungerstedt U. The striopallidal neuron: a main locus for adenosine-dopamine interactions in the brain. J Neurosci 1993; 13, 5402-5406.
27. Hillion J, Canals M, Torvinen M, et al. Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors. J Biol Chem 2002; 277: 18091-97.
28. Canals M, Marcellino D, Fanelli F, et al. Adenosine A2A-dopamine D2 receptor-receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 2003; 278: 46741-49.
29. Kamiya T, Saitoh O, Yoshioka K, Nakata H. Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Biochem Biophys Res Commun 2003; 306: 544-49.
30. Ciruela F, Burgueno J, Casado V. et al. Combining mass spectrometry and pull-down techniques for the study of receptor heteromerization. Direct epitope-epitope electrostatic interactions between adenosine A2A and dopamine D2 receptors. Anal Chem 2004; 76: 5354-63.
31. Woods AS, Ferré S. Amazing stability of the arginine-phosphate electrostatic interaction. J Proteome Res. 2005; 4: 1397-402.
32. Yao L, Arolfo MP, Dohrman DP, et al. Betagamma Dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signaling and regulate ethanol consumption. Cell 2002; 109: 733-43.
33. Kudlacek O, Just H, Korkhov VM, et al. The human D2 dopamine receptor synergizes with the A2A adenosine receptor to stimulate adenylyl cyclase in PC12 cells. Neuropsychopharmacology 2003; 28: 1317-27.
34. Vortherms TA, Watts VJ. Sensitization of neuronal A2A adenosine receptors after persistent D2 dopamine receptor activation. J Pharmacol Exp Ther 2004; 308: 221-27.
35. Chern Y. Regulation of adenylyl cyclase in the central nervous system. Cell Signal. 2000; 12: 195-204.
36. Defer N, Best-Belpomme M, Hanoune J. Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase. Am J Physiol Renal Physiol 2000; 279: F400-16.
37. Lee KW, Hong JH, Choi IY, et al. Impaired D2 dopamine receptor function in mice lacking type 5 adenylyl cyclase. J Neurosci 2002; 22: 7931-40.
38. Le Moine C, Svenningsson P, Fredholm BB, Bloch B. Dopamine-adenosine interactions in the striatum and the globus pallidus: inhibition of striatopallidal neurons through either D2 or A2A receptors enhances D1 receptor-mediated effects on c-fos expression. J Neurosci 1997; 17: 8038-48.
39. Pinna A, Wardas J, Cristalli G, Morelli M. Adenosine A2A receptor agonists increase Fos-like immunoreactivity in mesolimbic areas. Brain Res 1997; 759: 41-49.
40. Aoyama S, Koga K, Mori A, et al. Distribution of adenosine A(2A) receptor antagonist KW-6002 and its effect on gene expression in the rat brain. Brain Res 2002; 953: 119-25.
41. Carta AR, Tabrizi MA, Baraldi PG, et al. Blockade of A2A receptors plus 1-DOPA after nigrostriatal lesion results in GAD67 mRNA changes different from 1-DOPA alone in the rat globus pallidus and substantia nigra reticulata. Exp Neurol 2003; 184: 679-87.
42. Karcz-Kubicha M, Quarta D, Hope BT, et al. Enabling role of adenosine A1 receptors in adenosine A2A receptor-mediated striatal expression of c-fos. Ent J Neurosci 2003; 18: 296-302.
43. Wardas J, Pietraszek M, Dziedzicka-Wasylewska M. SCH 58261, a selective adenosine A2A receptor antagonist, decreases the haloperidol-enhanced proenkephalin mRNA expression in the rat striatum. Brain Res 2003; 977: 270-77.
44. Ferré S, Karcz-Kubicha M, Hope BT, et al. Synergistic interaction between adenosine A2A and glutamate mGlu5 receptors: implications for striatal neuronal function. Proc. Natl. Acad. Sci. USA 2002; 99: 11940-45.
45. Quarta D, Borycz J, Solinas M, et al. Adenosine receptor-mediated modulation of dopamine release in the nucleus accumbens depends on glutamate neurotransmission and N-methyl-D-aspartate receptor stimulation. J Neurochem 2004; 91: 873-80.
46. 2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation. J Neurosci 2006; 26: 10808-12.
47. Gerfen CR, Miyachi S, Paletzki R, Brown P. D1 dopamine receptor supersensitivity in the dopamine-depleted striatum results from a switch in the regulation of ERK1/2/MAP kinase. J Neurosci 2002; 22: 5042-54.
48. Calon F, Grondin R, Morissette M, et al. Molecular basis of levodopa-induced dyskinesias. Ann Neurol 2000; 47: S70-S78.
49. Jenner P. Factors influencing the onset and persistence of dyskinesia in MPTP-treated primates. Ann Neurol 2000; 47: S90-S99.
50. Obeso JA, Olanow CW, Nutt JG. Levodopa motor complications in Parkinson's disease. Trends Neurosci 2000; 23: S2-S7.
51. Rajput AH, Fenton ME, Birdi S, et al. Clinical-pathological study of levodopa complications. Mov Disord 2002; 17, 289-96.
52. Bordet R, Ridray S, Carboni S, et al. Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa. Proc Natl Acad Sci USA 1997; 94: 3363-37.
53. Cenci MA, Lee CS, Bjorklund A. L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur J Neurosci 1998; 10: 2694-706.
54. Henry B, Duty S, Fox SH, Crossman AR, Brotchie JM. Increased striatal pre-proenkephalin B expression is associated with dyskinesia in Parkinson's disease. Exp Neurol 2003; 183: 458-68.
55. Kanda T, Shiozaki S, Shimada J, Suzuki F, Nakamura J. KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity. Eur J Pharmacol 1994; 256: 263-68.
56. Pollack AE, Fink JS. Adenosine antagonists potentiate D2 dopamine-dependent activation of Fos in the striatopallidal pathway. Neuroscience 1995; 68: 721-28.
57. Shiozaki S, Ichikawa S, Nakamura J, et al. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology 1999; 147: 90-95.
58. Ward RP, Dorsa DM. Molecular and behavioral effects mediated by Gs-coupled adenosine A2a, but not serotonin 5-HT4 or 5-HT6 receptors following antipsychotic administration. Neuroscience 1999; 89: 927-38.
59. Chen JF, Moratalla R, Impagnatiello F, et al. The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice. Proc Natl Acad Sci USA 2001; 98: 1970-75.
60. Ferré S, Popoli P, Gimenez-Llort L, et al. Adenosine /dopamine interaction: implications for the treatment of Parkinson's disease. Parkinsonism Relat Disord 2001; 7: 235-41.
61. Hauber W, Neuscheler P, Nagel J, Muller CE. 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: 1287-93.
62. Wardas J, Konieczny J, Lorenc-Koci E. SCH 58261, an A(2A) adenosine receptor antagonist, counteracts parkinsonian-like muscle rigidity in rats. Synapse 2001; 41: 160-71.
63. Kanda, T., Jackson, M.J., Smith, L.A., et al. Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 1998; 43: 507-13.
64. Grondin R, Bedard PJ, Hadj Tahar A, et al. Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 1999; 52: 1673-77.
65. Ferré S, Fuxe K, von Euler G, Johansson B, Fredholm BB. Adenosine-dopamine interactions in the brain. Neuroscience 1992; 51: 501-12.
66. Pinna A, di Chiara G, Wardas J, Morelli M. Blockade of A(2a) adenosine receptors positively modulates turning behaviour and c-Fos expression induced by D1 agonists in dopamine-denervated rats. Eur J Neurosci 1996; 8: 1176-81.
67. Stromberg I, Popoli P, Muller CE, Ferré S, Fuxe K. Electrophysiological and behavioural evidence for an antagonistic modulatory role of adenosine A2A receptors in dopamine D2 receptor regulation in the rat dopamine-denervated striatum. Eur J Neurosci 2000; 12: 4033-37.
68. Ochi M, Koga K, Kurokawa M, et al. Systemic administration of adenosine A(2A) receptor antagonist reverses increased GABA release in the globus pallidus of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study. Neuroscience 2000; 100: 53-62.
69. Zahniser NR, Simosky JK, Mayfield RD, et al. Functional uncoupling of adenosine A(2A) receptors and reduced responseto caffeine in mice lacking dopamine D2 receptors. J Neurosci 2000; 20: 5949-57.
70. Fenn S, Pinna A, Ongini E, Morelli M. Adenosine A2A receptor antagonism potentiates L-DOPA-induced turning behaviour and c-fos expression in 6-hydroxydopamine-lesioned rats. Eur J Pharmacol 1997; 321: 143-47.
71. Kanda T, Jackson, MJ, Smith LA, 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: 321-27.
72. Koga K, Kurokawa M, Ochi M, Nakamura J, Kuwana Y. Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats. Eur J Pharmacol 2000; 408: 249-55.
73. Popoli P, Reggio R, Pezzola A. Effects of SCH 58261, an adenosine A(2A) receptor antagonist, on quinpirole-induced turning in 6-hydroxydopamine-lesioned rats. Lack of tolerance after chronic caffeine intake. Neuropsychopharmacology 2000; 22: 522-29.
74. Jenner P. Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease. Expert Opin Investig Drugs 2005; 14: 729-38.
75. Bara-Jimenez W, Sherzai A, Dimitrova T, et al. Adenosine A(2A) receptor antagonist treatment of Parkinson's disease. Neurology 2003; 61: 293-96.
76. Hauser RA, Hubble JP, Truong DD. Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology 2003; 61: 297-303.
77. Lee FS, Chao MV. Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc Natl Acad Sci USA 2001; 98: 3555-60.
78. Behan WM, Stone TW. Enhanced neuronal damage by co-administration of quinolinic acid and free radicals, and protection by adenosine A2A receptor antagonists. Br J Pharmacol 2002; 135: 1435-42.
79. Cassada DC, Tribble CG, Long SM, et al. Adenosine A2A agonist reduces paralysis after spinal cord ischemia: correlation with A2A receptor expression on motor neurons. Ann Thorac Surg 2002; 74: 846-49.
80. Popoli P, Pintor A, Domenici MR, et al. 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 2002; 22: 1967-75.
81. Blum D, Galas MC, Pintor A, et al. A dual role of adenosine A2A receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A2A antagonists. J Neurosci 2003; 23: 5361-69.
82. Marcoli M, Bonfanti A, Roccatagliata P, et al. Glutamate efflux from human cerebrocortical slices during ischemia: vesicular-like mode of glutamate release and sensitivity to A(2A) adenosine receptor blockade. Neuropharmacology 2004; 47: 884-91.
83. Blum D, Hourez R, Galas MC, Popoli P, Schiffmann SN. Adenosine receptors and Huntington's disease: implications for pathogenesis and therapeutics. Lancet Neurol 2003; 2: 366-74.
84. Schwarzschild MA, Xu K, Oztas E, et al. Neuroprotection by caffeine and more specific A2A receptor antagonists in animal models of Parkinson's disease. Neurology 2003; 61:S55-61.
85. Popoli P, Minghetti L, Tebano MT, et al. Adenosine A2A receptor antagonism and neuroprotection: mechanisms, lights, and shadows. Crit Rev Neurobiol 2004; 16: 99-106.
86. Chen JF, Xu K, Petzer JP, et al. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinsons disease. J Neurosci 2001; 21: RC143.
87. Ikeda K, Kurokawa M, Aoyama S, Kuwana Y. Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson's disease. J Neurochem 2002 Jan; 80: 262-70.
88. Fredduzzi S, Moratalla R, Monopoli A, et al. Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors. J Neurosci 2002; 22:1054-62.
89. Agnati LF, Leo G, Vergoni AV, et al. Neuroprotective effect of L-DOPA co-administered with the adenosine A2A receptor agonist CGS 21680 in an animal model of Parkinson's disease. Brain Res Bull 2004; 64: 155-64.
90. Petzer JP, Steyn S, Castagnoli KP, et al. Inhibition of monoamine oxidase B by selective adenosine A2A receptor antagonists. Bioorg Med Chem 2003; 11: 1299-310.
91. 2A receptor antagonists. Farmaco 2001; 56: 87-90.
92. 2A adenosine receptor antagonists. Curr Top Med Chem 2003; 3: 403-11.
93. Müller CE, Scior T. Adenosine receptors and their modulators. Pharm Acta Helv 1993; 68: 77-111.
94. 2A adenosine receptor antagonists - future drugs for Parkinson's disease? Drugs Fut 2000; 25: 1043-52.
95. Müller CE, Stein B. Adenosine receptor antagonists: structures and potential therapeutic applications. Curr Pharm Des 1996; 2: 501-530.
96. 3 adenosine receptor ligands. Eur J Med Chem 2003; 38: 367-382.
97. Kiec-Kononowicz K, Drabczynska A, Pekala E, et al. Pure Appl Chem 2001; 73: 1411-20.
98. 2A receptor antagonists. Curr Opin Drug Discov Devel 2005; 8: 458-68.
99. Seale TW, Abla KA, Shamim MT, Carney JM, Daly JW. 3,7-Dimethyl-1-propargylxanthine: a potent and selective in vivo antagonist of adenosine analogs. Life Sci 1988; 43: 1671-84.
100. Jacobson KA, Ukena D, Kirk KL, Daly JW. [3H]Xanthine amine congener of 1,3-dipropyl-8-phenylxanthine: an antagonist radioligand for adenosine receptors. Proc Natl Acad Sci USA 1986; 83: 4089-93.
101. Shamim MT, Ukena D, Padgett WL, Daly JW. Effects of 8-phenyl and 8-cycloalkyl substituents on the activity of mono-, di-, and trisubstituted alkylxanthines with substitution at the 1-, 3-, and 7-positions. J Med Chem 1989; 32, 1231-37.
102. 2 affinity. J Med Chem 1991; 34: 1431-35.
103. 2A-adenosine receptor antagonists. Eur J Med Chem 1997; 32: 709-19.
104. 2-selective adenosine antagonists. J Med Chem 1993; 36: 1333-42.
105. Kase H, Aoyama S, Ichimura M, et al. KW-6002 US-001 Study Group. 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 2003; 61: S97-100.
106. 2A-selective adenosine receptor antagonists. J Med Chem 1997; 40: 4396-405.
107. 2A-selective adenosine receptor antagonists. J Med Chem 2000; 43: 440-48.
108. 2A adenosine receptor antagonists with 8-styrylxanthine structure: potential drugs for Parkinson's disease. J Org Chem 2004; 69: 3308-18.
109. 2A adenosine receptor antagonists. Bioorg Med Chem 2006; 14: 2697-2719.
110. 2A receptor antagonism. J Biol Chem 2002; 277: 36040-44.
111. 2A receptor antagonist (E)-8-3-chlorostyryl)caffeine (CSC). Bioorg Med Chem 2006; 14: 3512-21.
112. Nonaka Y, Shimada J, Nonaka H, et al. Photoisomerization of a potent and selective adenosine A2 antagonist, (E)-1,3-dipropyl-8-(3,4-dimethoxystyryl)-7-methylxanthine. J Med Chem 1993; 36: 3731-33.
113. 2A receptors in the caudate-putamen. Neuroreport 1998; 9: 1803-1806.
114. 2 receptors. Neurosci Lett 2002; 324: 154-58.
115. 2A receptor blockade in the nucleus accumbens on locomotion, feeding, and prepulse inhibition in rats. Synapse 2003; 49: 279-86.
116. 2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. J Pharmacol Exp Ther 2003; 307: 977-86.
117. 2A receptor agonist CGS 21680. Eur J Pharmacol 2004; 484: 269-75.
118. 1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion. J Neurochem 2004; 90: 621-28.
119. 2A receptors on glutamate and dopamine release in the shell of the nucleus accumbens. Effects of chronic caffeine exposure. J Neurochem 2004; 88: 1151-58.
120. 2A subtype receptor agonists. Br J Pharmacol 2005; 144: 642-50.
121. 1 receptors in the discriminative-stimulus effects of caffeine in rats. Psychopharmacology 2005; 179: 576-86.
122. 2A receptors. Psychopharmacology 2005; 183: 154-62.
123. 2A and dopamine receptors in the locomotor and sensitizing effects of cocaine. Brain Res 2006; 1077: 67-80.
124. Farrar AM, Pereira M, Velasco F, et al. Adenosine A2A receptor antagonism reverses the effects of dopamine receptor antagonism on instrumental output and effort-related choice in the rat: implications for studies of psychomotor slowing. Psychopharmacology 2006, in press.
125. Drabczynska A, Schumacher B, Müller CE, et al. Irnpact of the aryl substituent kind and distance from pyrimido[2,1-f]purindiones on the adenosine receptor selectivity and antagonistic properties. Eur J Med Chem 2003; 38: 397-402.
126. 1 receptor antagonists: xanthines modified at position 3 and related pyrimido[1,2,3-cd]purinediones. Chem Med Chem 2006; 1: 891-902.
127. 3 receptor ligands. Curr Top Med Chem 2003; 3: 445-62.
128. Bulicz J, Bertarelli DCG, Baumert D, et al. Synthesis and pharmacology of pyrido[2,3-d]pyrimidinediones bearing polar substituents as adenosine reeptor antagnists. Bioorg Med Chem 2006; 14: 2837-49.
129. Camaioni E, Costanzi S, Vittori S, et al. New substituted 9-alkylpurines as adenosine receptor ligands. Bioorg Med Chem 1998; 6: 523-33.
130. Klotz KN, Kachler S, Lambertucci C, et al. G. 9-Ethyladenine derivatives as adenosine receptor antagonists: 2- and 8-substitution results in distinct selectivites. Naunyn-Schmiedeberg's Arch Pharmacol 2003; 367: 629-34.
131. 2A receptor antagonists: actions on Parkinson's disease models. Eur J Pharmacol 2005; 512: 157-64.
132. Beauglehole, A., Rieger, J.M., Thompson, R.D.: WO05097140A2 (2005).
133. Yan L, Burbiel JC, Maass A, Müller CE. Adenosine receptor agonists: from basic medicinal chemistry to clinical development. Exp Opin Emerg Drugs 2003; 8: 537-76.
134. 2A adenosine receptor antagonists. Design, synthesis, and phramacological characterization. J Med Chem 2005; 48: 6887-6896.
135. Daly JW, Padgett WL, Eger K. 7-Deaza-9-phenyladenines. A new class of adenosine receptor antagonists. Biochem Pharmacol 1988; 37: 3749-53.
136. Müller CE, Geis U, Grahner B, Lanzner W, Eger K. Chiral pyrrolo[2,3-d]pyrimidine and pyrimidio[4,5-b]indole derivatives: structure-activity relationships of potent, highly stereoselective A1-adenosine receptor antagonists. J Med Chem 1996; 39: 2482-91.
137. 1 selective adenosine receptor antagonists. J Med Chem 1990; 33: 2822-28.
138. 3 adenosine receptor antagonists. J Med Chem 2000; 43: 4636-46.
139. Castelhano, A.L., McKibben, B., Witter, D.J.: US20036664252B2 (2003).
140. 2A adenosine receptor antagonists for positron emission tomography (PET). Eur J Med Chem 2006; 41: 7-15.
141. 2A adenosine antagonists. Bioorg Med Chem 2005; 15: 2119-22.
142. 2A receptor antagonists for the treatment of Parkinson's disease. Neurology 2003: 61 (Suppl. 6): S101-106.
143. Gillespie, R.J., Lerpinier, J.: WO02055094A1 (20020).
144. Gillespie, R.J., Lerpiniere, J., Gaur, S.: US20060111373A1 (2006).
145. 1 receptor antagonists. J Med Chem 1996; 39: 4156-61.
146. 2A-antagonistic effect). Pharmazie 2005; 60: 732-35.
147. Gillespie, R.J., Giles, P.R., Lerpiniere, J., Dawson, C.E., Bebbington, D.W.O.: WO0102409A1 (2001).
148. 2A Receptors in Parkinson's Disease and Other CNS Disorders. Boston, USA 2006.
149. 2A Receptors in Parkinson's Disease and Other CNS Disorders. Boston, USA 2006.
150. 2A Receptors in Parkinson's Disease and Other CNS Disorders. Boston, USA 2006.
151. Crespo, M.I., Prat, Q. M., Gual, R.S., Castro, P. L.J.C., Slee, D.H.: WO058883A1 (2005).
152. Akahane, A.: WO04016605A1 (2004).
153. Harada, H., Asano, O., Ueda, M., Miyazawa, S., Kotake, Y., Kabasawa, Y., Yasuda, M., Yasuda, N., Iida, D., Nagakawa, J., Hirota, K., Nakagawa, M.: WO03035639A1 (2003), US 20050004149A1 (2005).
154. Borroni, M.E., Huber-, T.G., Kilpatrick, J.G.E., Norcross, D.R.: US20036586441 B2 (2003), WO01062233, EP1261327B1 (2005).
155. 2A adenosine antagonists. J Med Chem 1996; 39: 1164-71.
156. 2A adenosine receptor antagonists: a study on the importance of modifications at the side chain on the activity and solubility. J Med Chem 2002; 45: 115-26.
157. Neustadt, B.R., Lino, N.: US20050026932A1 (2005).
158. Neustadt, B.R., Hao, J., Liu, H., Neustadt, B. R., Hao, J., Liu, H., Boyle, C.D., Chackalamannil, S., Shah, U.G., Stamford, A., Harris, J. M.: WO05103055A1 (2005).
159. Neustadt, B.R., Hao, J., Boyle, C.D., Neustadt B. R., Hao, J., Liu, H., Boyle, C.D., Chackalamannil, S., Shah, U.G., Stamford, A.: WO04094431A3 (2004).
160. Grzelak, M., Hunter, J., Pond, A., Varty, G.: US20040138235 (2004).
161. Neustadt, B.R., Lindo, N., Greenlee, W.J., Lindo, N., Greenlee, W.J., Tulshian,D., Silverman, L. S, Xia, Y., Boyle, C.D., Chackalamannil, S.: US20040023997A1 (2004).
162. 2A Receptors in Parkinson's Disease and Other CNS Disorders. Boston, USA 2006.
163. 2A Receptors in Parkinson's Disease and Other CNS Disorders. Boston, USA 2006.
164. 2A Receptors in Parkinson's Disease and Other CNS Disorders. Boston, USA 2006.
165. 2A receptor antagonists. J Med Chem 2004; 47: 4291-4299.
166. 2A receptor antagonists. J Med Chem 2005; 48: 2009-18.
167. 2A receptor antagonists. J Med Chem 2004; 47: 6218-6229.
168. 2A receptor antagonists. Bioorg Med Chem Lett 2004; 14: 4835-38.
169. Vu CB, Pan D, Peng B, et al. Studies on adenosine A2A receptor antagonists: comparison of three core heterocycles. Bioorg Med Chem Lett 2004; 14: 4831-34.
170. Vu, C., Petter, R.C., Kumaravel, G.: WO04092170A2 (2004).
171. Peng, H., Yao, G., Petter, R., Kumaravel, G.: WO04092173A3 (2004.
172. Hiroshi, T., Shimada, J., Imma, H.: US20016222035B1 (2001).
173. Iida, K., Sugita, T., Shiozaki S.: WO04029056 (2004).
174. Neustadt, B.R., Liu, H.: WO03048163 A1 (2003).
175. 2A antagonists. Part 1. Bioorg Med Chem Lett 2005; 15: 3670-3674.
176. 2A antagonists: the successful reduction of hERG activity. Part 2. Bioorg Med Chem Lett 2005; 15: 3675-78.
177. 2A adenosine receptor antagonists. Bioorg Med Chem Lett 2005; 15: 511-15.
178. 2A receptor antagonists. Bioorg Med Chem Lett 2005; 15, 4809-13.
179. 2A adenosine receptor antagonists. Bioorg Med Chem 2003; 11: 5509-18.
180. Holschbach MH, Bier D, Wutz W, et al. Derivatives of
181. Heintzelman, G.R., Bullington, J., Rupert K.C.: WO05042500A1 (2005).
182. 2A antagonists. Bioorg Med Chem Lett 2005; 15: 1333-36.
183. Alanine, A., Flohr, A., Miller, A.K., Norcross, R.D., Riemer, K.: WO01097786 (2001).
184. Alanine, A., Flohr, A., Miller, A.K., Norcross, R.D., Riemer, K.: US20060003986A1 (2006).
185. Norcross, R.D.: WO050028484A1 (2005).
186. 2A receptor antagonists. Bioorg Med Chem Lett 2004; 14: 817-21.
187. Westman, J., Norstedt, G.: WO0518532 A2 (2005).
188. Fredholm, B., Kull, B.: WO04058974A1 (2004).
189. Peterson LA, Cummings ME, Vu CC, Matter BA. Glutathione trapping to measure microsomal oxidation of firan to cis-2-butene-1,4-dial. Drug Metab Dispos 2005; 33: 1453-81.
190. 2A agonists and antagonists. J Med Chem 2003; 46: 4847-59.