Xanthine Derivatives as Agents Affecting Non-dopaminergic Neuroprotection in Parkinson’s Disease

Author(s): Alexandra Kasabova-Angelova, Diana Tzankova, Javor Mitkov, Maya Georgieva, Virginia Tzankova, Alexander Zlatkov, Magdalena Kondeva-Burdina*.

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 12 , 2020

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Parkinson's Disease (PD) is a neurodegenerative and debilitating disease that affects 1% of the elderly population. Patient’s motor disability results in extreme difficulty to deal with daily activities. Conventional treatment is limited to dopamine replacement therapy, which fails to delay disease’s progression and is often associated with a number of adverse reactions. Recent progress in understanding the mechanisms involved in PD has revealed new molecular targets for therapeutic approaches. Among them, caffeine and xanthine derivatives are promising drug candidates, because of the possible symptomatic benefits in PD. In fact, consumption of coffee correlates with a reduced risk of PD. Over the last decades, a lot of efforts have been made to uncover the therapeutic potential of xanthine structures. The substituted xanthine molecule is used as a scaffold for the synthesis of new compounds with protective effects in neurodegenerative diseases, including PD, asthma, cancer and others. The administration of the xanthines has been proposed as a non-dopaminergic strategy for neuroprotection in PD and the mechanisms of protection have been associated with antagonism of adenosine A2A receptors and Monoamine Oxidase type B (MAO-B) inhibition. The current review summarizes frequently suspected non-dopaminergic neuroprotective mechanisms and the possible beneficial effects of the xanthine derivatives in PD, along with some synthetic approaches to produce perspective xanthine derivatives as non-dopaminergic agents in PD treatment.

Keywords: Xanthines, caffeine, Parkinson’s disease, neuroprotection, neurodegeneration, non-dopaminergic approach.

Blaylock, R. L. Parkinson's disease: Microglial/ macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration Surg Neurol Int., 2017, 26, 8:65.
Dauer, W.; Przedborski, S. Parkinson’s disease: mechanisms and models. Neuron, 2003, 39(6), 889-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
Beal, M.F. Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann. N. Y. Acad. Sci., 2003, 991, 120-131.
[http://dx.doi.org/10.1111/j.1749-6632.2003.tb07470.x] [PMID: 12846981]
Henchcliffe, C.; Beal, M.F. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat. Clin. Pract. Neurol., 2008, 4(11), 600-609.
[http://dx.doi.org/10.1038/ncpneuro0924] [PMID: 18978800]
Taylor, J.M.; Main, B.S.; Crack, P.J. Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson’s disease. Neurochem. Int., 2013, 62(5), 803-819.
[http://dx.doi.org/10.1016/j.neuint.2012.12.016] [PMID: 23291248]
Dunet, V.; Deverdun, J.; Charroud, C.; Le Bars, E.; Molino, F.; Menjot de Champfleur, S.; Maury, F.; Charif, M.; Ayrignac, X.; Labauge, P.; Castelnovo, G.; Pinna, F.; Bonafe, A.; Geny, C.; Menjot de Champfleur, N. Cognitive Impairment and Basal Ganglia Functional Connectivity in Vascular Parkinsonism. AJNR Am. J. Neuroradiol., 2016, 37(12), 2310-2316.
[http://dx.doi.org/10.3174/ajnr.A4889] [PMID: 27418471]
Ahlskog, J.E.; Muenter, M.D. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov. Disord., 2001, 16(3), 448-458.
[http://dx.doi.org/10.1002/mds.1090] [PMID: 11391738]
Allain, H.; Bentué-Ferrer, D.; Akwa, Y. Disease-modifying drugs and Parkinson’s disease. Prog. Neurobiol., 2008, 84(1), 25-39.
[http://dx.doi.org/10.1016/j.pneurobio.2007.10.003] [PMID: 18037225]
Song, B.; Xiao, T.; Qi, X.; Li, L.N.; Qin, K.; Nian, S.; Hu, G.X.; Yu, Y.; Liang, G.; Ye, F. Design and synthesis of 8-substituted benzamido-phenylxanthine derivatives as MAO-B inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(4), 1739-1742.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.094] [PMID: 22257893]
Fernandez, H.H.; Greeley, D.R.; Zweig, R.M.; Wojcieszek, J.; Mori, A.; Sussman, N.M. 6002-US-051 Study Group. Istradefylline as monotherapy for Parkinson disease: results of the 6002-US-051 trial. Parkinsonism Relat. Disord., 2010, 16(1), 16-20.
[http://dx.doi.org/10.1016/j.parkreldis.2009.06.008] [PMID: 19616987]
Schapira, A.H.; Bezard, E.; Brotchie, J.; Calon, F.; Collingridge, G.L.; Ferger, B.; Hengerer, B.; Hirsch, E.; Jenner, P.; Le Novère, N.; Obeso, J.A.; Schwarzschild, M.A.; Spampinato, U.; Davidai, G. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat. Rev. Drug Discov., 2006, 5(10), 845-854.
[http://dx.doi.org/10.1038/nrd2087] [PMID: 17016425]
Ferré, S.; Bonaventura, J.; Tomasi, D.; Navarro, G.; Moreno, E.; Cortés, A.; Lluís, C.; Casadó, V.; Volkow, N.D. Allosteric mechanisms within the adenosine A2A-dopamine D2 receptor heterotetramer. Neuropharmacology, 2016, 104, 154-160.
[http://dx.doi.org/10.1016/j.neuropharm.2015.05.028] [PMID: 26051403]
Ferreira, D.G.; Batalha, V.L.; Vicente Miranda, H.; Coelho, J.E.; Gomes, R.; Gonçalves, F.Q.; Real, J.I.; Rino, J.; Albino-Teixeira, A.; Cunha, R.A.; Outeiro, T.F.; Lopes, L.V. Adenosine A2A Receptors Modulate α-Synuclein Aggregation and Toxicity. Cereb. Cortex, 2017, 27(1), 718-730.
[PMID: 26534909]
de Souza, M.F.; Bispo, J.M.M.; Leal, P.C.; de Gois, A.M.; Dos Santos, J.R. Commentary: Adenosine A2A Receptor Blockade Prevents Rotenone-Induced Motor Impairment in a Rat Model of Parkinsonism. Front. Behav. Neurosci., 2017, 11, 93.
[http://dx.doi.org/10.3389/fnbeh.2017.00093] [PMID: 28579949]
Fernández-Dueñas, V.; Pérez-Arévalo, A.; Altafaj, X.; Ferré, S.; Ciruela, F. Adenosine A1-A2A Receptor Heteromer as a Possible Target for Early-Onset Parkinson's Disease., Front Neurosci, 2017, 22, 11:652.
Vorovenci, R.J.; Antonini, A. The efficacy of oral adenosine A(2A) antagonist istradefylline for the treatment of moderate to severe Parkinson’s disease. Expert Rev. Neurother., 2015, 15(12), 1383-1390.
[http://dx.doi.org/10.1586/14737175.2015.1113131] [PMID: 26630457]
Fathalla, A.M.; Soliman, A.M.; Moustafa, A.A. Selective A2A receptors blockade reduces degeneration of substantia nigra dopamine neurons in a rotenone-induced rat model of Parkinson’s disease: A histological study. Neurosci. Lett., 2017, 643, 89-96.
[http://dx.doi.org/10.1016/j.neulet.2017.02.036] [PMID: 28213070]
Tian, S.; Wang, X.; Li, L.; Zhang, X.; Li, Y.; Zhu, F.; Hou, T.; Zhen, X. Discovery of Novel and Selective Adenosine A2A Receptor Antagonists for Treating Parkinson’s Disease through Comparative Structure-Based Virtual Screening. J. Chem. Inf. Model., 2017, 57(6), 1474-1487.
[http://dx.doi.org/10.1021/acs.jcim.7b00188] [PMID: 28463561]
Reyhani-Rad, S.; Mahmoudi, J. Effect of adenosine A2A receptor antagonists on motor disorders induced by 6-hydroxydopamine in rat. Acta Cir. Bras., 2016, 31(2), 133-137.
[http://dx.doi.org/10.1590/S0102-865020160020000008] [PMID: 26959623]
Pinna, A.; Fenu, S.; Morelli, M. Motor stimulant effects of the adenosine A2A receptor antagonist SCH 58261 do not develop tolerance after repeated treatments in 6-hydroxydopamine-lesioned rats. Synapse, 2001, 39(3), 233-238.
[http://dx.doi.org/10.1002/1098-2396(20010301)39:3<233:AID-SYN1004>3.0.CO;2-K] [PMID: 11284438]
Kanda, T.; Jackson, M.J.; Smith, L.A.; Pearce, R.K.; Nakamura, J.; Kase, H.; Kuwana, Y.; Jenner, P. Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann. Neurol., 1998, 43(4), 507-513.
[http://dx.doi.org/10.1002/ana.410430415] [PMID: 9546333]
Grondin, R.; Bédard, P.J.; Hadj Tahar, A.; Grégoire, L.; Mori, A.; Kase, H. Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology, 1999, 52(8), 1673-1677.
[http://dx.doi.org/10.1212/WNL.52.8.1673] [PMID: 10331698]
Kanda, T.; Jackson, M.J.; Smith, L.A.; Pearce, R.K.; Nakamura, J.; Kase, H.; Kuwana, Y.; Jenner, P. 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(2), 321-327.
[http://dx.doi.org/10.1006/exnr.2000.7350] [PMID: 10739638]
Stayte, S.; Vissel, B. Advances in non-dopaminergic treatments for Parkinson’s disease. Front. Neurosci., 2014, 8, 113.
[http://dx.doi.org/10.3389/fnins.2014.00113] [PMID: 24904259]
Xu, K.; Bastia, E.; Schwarzschild, M. Therapeutic potential of adenosine A(2A) receptor antagonists in Parkinson’s disease. Pharmacol. Ther., 2005, 105(3), 267-310.
[http://dx.doi.org/10.1016/j.pharmthera.2004.10.007] [PMID: 15737407]
Lebois, E. P.; Thorn, C.; Edgerton, J. R.; Popiolek, M.; Xi, S. Muscarinic receptor subtype distribution in the central nervous system and relevance to aging and Alzheimer's disease, Neuropharmacology, 2017, S0028-3908. (17)30527-0
Bouvier, G.; Bidoret, C.; Casado, M.; Paoletti, P. Presynaptic NMDA receptors: Roles and rules. Neuroscience, 2015, 311, 322-340.
[http://dx.doi.org/10.1016/j.neuroscience.2015.10.033] [PMID: 26597763]
Petzer, J.P.; Castagnoli, N., Jr; Schwarzschild, M.A.; Chen, J.F.; Van der Schyf, C.J. Dual-target-directed drugs that block monoamine oxidase B and adenosine A(2A) receptors for Parkinson’s disease. Neurotherapeutics, 2009, 6(1), 141-151.
[http://dx.doi.org/10.1016/j.nurt.2008.10.035] [PMID: 19110205]
Petzer, J.P.; Steyn, S.; Castagnoli, K.P.; Chen, J.F.; Schwarzschild, M.A.; Van der Schyf, C.J.; Castagnoli, N. Inhibition of monoamine oxidase B by selective adenosine A2A receptor antagonists. Bioorg. Med. Chem., 2003, 11(7), 1299-1310.
[http://dx.doi.org/10.1016/S0968-0896(02)00648-X] [PMID: 12628657]
Azam, F.; Madi, A.M.; Ali, H.I. Molecular Docking and Prediction of Pharmacokinetic Properties of Dual Mechanism Drugs that Block MAO-B and Adenosine A(2A) Receptors for the Treatment of Parkinson’s Disease. J. Young Pharm., 2012, 4(3), 184-192.
[http://dx.doi.org/10.4103/0975-1483.100027] [PMID: 23112538]
Fredholm, B.B. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ., 2007, 14(7), 1315-1323.
[http://dx.doi.org/10.1038/sj.cdd.4402132] [PMID: 17396131]
Di Virgilio, F.; Adinolfi, E. Extracellular purines, purinergic receptors and tumor growth. Oncogene, 2017, 36(3), 293-303.
[http://dx.doi.org/10.1038/onc.2016.206] [PMID: 27321181]
Deussen, A.; Schrader, J. Cardiac adenosine production is linked to myocardial pO2. J. Mol. Cell. Cardiol., 1991, 23(4), 495-504.
[http://dx.doi.org/10.1016/0022-2828(91)90173-J] [PMID: 1942083]
Jonzon, B.; Fredholm, B.B. Release of purines, noradrenaline, and GABA from rat hippocampal slices by field stimulation. J. Neurochem., 1985, 44(1), 217-224.
[http://dx.doi.org/10.1111/j.1471-4159.1985.tb07133.x] [PMID: 3964829]
Ma, Y.; Zhang, J.; Zhang, Q.; Chen, P.; Song, J.; Yu, S.; Liu, H.; Liu, F.; Song, C.; Yang, D.; Liu, J. Adenosine induces apoptosis in human liver cancer cells through ROS production and mitochondrial dysfunction. Biochem. Biophys. Res. Commun., 2014, 448(1), 8-14.
[http://dx.doi.org/10.1016/j.bbrc.2014.04.007] [PMID: 24727456]
Linden, J. Adenosine in tissue protection and tissue regeneration. Mol. Pharmacol., 2005, 67(5), 1385-1387.
[http://dx.doi.org/10.1124/mol.105.011783] [PMID: 15703375]
Fredholm, B.B.; Bättig, K.; Holmén, J.; Nehlig, A.; Zvartau, E.E. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol. Rev., 1999, 51(1), 83-133.
[PMID: 10049999]
Kalda, A.; Yu, L.; Oztas, E.; Chen, J.F. Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson’s disease. J. Neurol. Sci., 2006, 248(1-2), 9-15.
[http://dx.doi.org/10.1016/j.jns.2006.05.003] [PMID: 16806272]
Ferré, S.; von Euler, G.; Johansson, B.; Fredholm, B.B.; 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(16), 7238-7241.
[http://dx.doi.org/10.1073/pnas.88.16.7238] [PMID: 1678519]
Svenningsson, P.; Le Moine, C.; Fisone, G.; Fredholm, B.B. Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog. Neurobiol., 1999, 59(4), 355-396.
[http://dx.doi.org/10.1016/S0301-0082(99)00011-8] [PMID: 10501634]
Shook, B.C.; Rassnick, S.; Osborne, M.C.; Davis, S.; Westover, L.; Boulet, J.; Hall, D.; Rupert, K.C.; Heintzelman, G.R.; Hansen, K.; Chakravarty, D.; Bullington, J.L.; Russell, R.; Branum, S.; Wells, K.M.; Damon, S.; Youells, S.; Li, X.; Beauchamp, D.A.; Palmer, D.; Reyes, M.; Demarest, K.; Tang, Y.; Rhodes, K.; Jackson, P.F. In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson’s disease. J. Med. Chem., 2010, 53(22), 8104-8115.
[http://dx.doi.org/10.1021/jm100971t] [PMID: 20973483]
Kachroo, A.; Schwarzschild, M.A. Adenosine A2A receptor gene disruption protects in an α-synuclein model of Parkinson’s disease. Ann. Neurol., 2012, 71(2), 278-282.
[http://dx.doi.org/10.1002/ana.22630] [PMID: 22367999]
Chen, J.F. The adenosine A(2A) receptor as an attractive target for Parkinson’s disease treatment. Drug News Perspect., 2003, 16(9), 597-604.
[http://dx.doi.org/10.1358/dnp.2003.16.9.829342] [PMID: 14702141]
Orr, A.G.; Lo, I.; Schumacher, H.; Ho, K.; Gill, M.; Guo, W.; Kim, D.H.; Knox, A.; Saito, T.; Saido, T.C.; Simms, J.; Toddes, C.; Wang, X.; Yu, G.Q.; Mucke, L. Istradefylline reduces memory deficits in aging mice with amyloid pathology. Neurobiol. Dis., 2018, 110, 29-36.
[http://dx.doi.org/10.1016/j.nbd.2017.10.014] [PMID: 29100987]
Dungo, R.; Deeks, E.D. Istradefylline: first global approval. Drugs, 2013, 73(8), 875-882.
[http://dx.doi.org/10.1007/s40265-013-0066-7] [PMID: 23700273]
Du, J.J.; Chen, S.D. Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson’s Disease. Chin. Med. J. (Engl.), 2017, 130(15), 1856-1866.
[http://dx.doi.org/10.4103/0366-6999.211555] [PMID: 28748860]
Chen, J.F.; Xu, K.; Petzer, J.P.; Staal, R.; Xu, Y.H.; Beilstein, M.; Sonsalla, P.K.; Castagnoli, K.; Castagnoli, N., Jr; Schwarzschild, M.A. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson’s disease. J. Neurosci., 2001, 21(10), RC143.
[http://dx.doi.org/10.1523/JNEUROSCI.21-10-j0001.2001] [PMID: 11319241]
Bibbiani, F.; Oh, J.D.; Petzer, J.P.; Castagnoli, N., Jr; Chen, J.F.; Schwarzschild, M.A.; Chase, T.N. A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease. Exp. Neurol., 2003, 184(1), 285-294.
[http://dx.doi.org/10.1016/S0014-4886(03)00250-4] [PMID: 14637099]
Chen, J.F.; Moratalla, R.; Impagnatiello, F.; Grandy, D.K.; Cuellar, B.; Rubinstein, M.; Beilstein, M.A.; Hackett, E.; Fink, J.S.; Low, M.J.; Ongini, E.; Schwarzschild, M.A. 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(4), 1970-1975.
[http://dx.doi.org/10.1073/pnas.98.4.1970] [PMID: 11172060]
Ross, G.W.; Abbott, R.D.; Petrovitch, H.; Morens, D.M.; Grandinetti, A.; Tung, K.H.; Tanner, C.M.; Masaki, K.H.; Blanchette, P.L.; Curb, J.D.; Popper, J.S.; White, L.R. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA, 2000, 283(20), 2674-2679.
[http://dx.doi.org/10.1001/jama.283.20.2674] [PMID: 10819950]
Madeira, M.H.; Boia, R.; Ambrósio, A.F.; Santiago, A.R. Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases. Mediators Inflamm., 2017, 20174761081
[http://dx.doi.org/10.1155/2017/4761081] [PMID: 28250576]
Westlund, K.N.; Denney, R.M.; Kochersperger, L.M.; Rose, R.M.; Abell, C.W. Distinct monoamine oxidase A and B populations in primate brain. Science, 1985, 230(4722), 181-183.
[http://dx.doi.org/10.1126/science.3875898] [PMID: 3875898]
Kalaria, R.N.; Mitchell, M.J.; Harik, S.I. Monoamine oxidases of the human brain and liver. Brain, 1988, 111(Pt 6), 1441-1451.
[http://dx.doi.org/10.1093/brain/111.6.1441] [PMID: 3208065]
Fowler, J.S.; Logan, J.; Volkow, N.D.; Wang, G.J.; MacGregor, R.R.; Ding, Y.S. Monoamine oxidase: radiotracer development and human studies. Methods, 2002, 27(3), 263-277.
[http://dx.doi.org/10.1016/S1046-2023(02)00083-X] [PMID: 12183115]
Levitt, P.; Pintar, J.E.; Breakefield, X.O. Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons. Proc. Natl. Acad. Sci. USA, 1982, 79(20), 6385-6389.
[http://dx.doi.org/10.1073/pnas.79.20.6385] [PMID: 6755469]
Shih, J.C.; Chen, K.; Ridd, M.J. Monoamine oxidase: from genes to behavior. Annu. Rev. Neurosci., 1999, 22, 197-217.
[http://dx.doi.org/10.1146/annurev.neuro.22.1.197] [PMID: 10202537]
Youdim, M.B.; Edmondson, D.; Tipton, K.F. The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci., 2006, 7(4), 295-309.
[http://dx.doi.org/10.1038/nrn1883] [PMID: 16552415]
Shih, J.C.; Wu, J.B.; Chen, K. Transcriptional regulation and multiple functions of MAO genes. J. Neural Transm. (Vienna), 2011, 118(7), 979-986.
[http://dx.doi.org/10.1007/s00702-010-0562-9] [PMID: 21359973]
Waldmeier, P.C. Amine oxidases and their endogenous substrates (with special reference to monoamine oxidase and the brain). J. Neural Transm. Suppl., 1987, 23, 55-72.
[http://dx.doi.org/10.1007/978-3-7091-8901-6_4] [PMID: 3108453]
Carradori, S.; Secci, D.; Bolasco, A.; Chimenti, P.; D’Ascenzio, M. Patent-related survey on new monoamine oxidase inhibitors and their therapeutic potential. Expert Opin. Ther. Pat., 2012, 22(7), 759-801.
[http://dx.doi.org/10.1517/13543776.2012.698613] [PMID: 22702491]
Collins, G.G.; Sandler, M.; Williams, E.D.; Youdim, M.B. Multiple forms of human brain mitochondrial monoamine oxidase. Nature, 1970, 225(5235), 817-820.
[http://dx.doi.org/10.1038/225817a0] [PMID: 5415111]
Birkmayer, W.; Riederer, P.; Youdim, M.B.; Linauer, W. The potentiation of the anti akinetic effect after L-dopa treatment by an inhibitor of MAO-B, Deprenil. J. Neural Transm. (Vienna), 1975, 36(3-4), 303-326.
[http://dx.doi.org/10.1007/BF01253131] [PMID: 1172524]
Di Monte, D.A.; DeLanney, L.E.; Irwin, I.; Royland, J.E.; Chan, P.; Jakowec, M.W.; Langston, J.W. Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of L-DOPA-treated monkeys. Brain Res., 1996, 738(1), 53-59.
[http://dx.doi.org/10.1016/0006-8993(96)00761-5] [PMID: 8949927]
Finberg, J.P.; Wang, J.; Bankiewicz, K.; Harvey-White, J.; Kopin, I.J.; Goldstein, D.S. Increased striatal dopamine production from L-DOPA following selective inhibition of monoamine oxidase B by R(+)-N-propargyl-1-aminoindan (rasagiline) in the monkey. J. Neural Transm. Suppl., 1998, 52, 279-285.
[http://dx.doi.org/10.1007/978-3-7091-6499-0_28] [PMID: 9564628]
Fernandez, H.H.; Chen, J.J. Monoamine oxidase-B inhibition in the treatment of Parkinson’s disease. Pharmacotherapy, 2007, 27(12 Pt 2), 174S-185S.
[http://dx.doi.org/10.1592/phco.27.12part2.174S] [PMID: 18041937]
Pålhagen, S.; Heinonen, E.; Hägglund, J.; Kaugesaar, T.; Mäki-Ikola, O.; Palm, R. Swedish Parkinson Study Group. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology, 2006, 66(8), 1200-1206.
[http://dx.doi.org/10.1212/01.wnl.0000204007.46190.54] [PMID: 16540603]
Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch. Neurol., 2005, 62(2), 241-248.
[http://dx.doi.org/10.1001/archneur.62.2.241] [PMID: 15710852]
Gesi, M.; Santinami, A.; Ruffoli, R.; Conti, G.; Fornai, F. Novel aspects of dopamine oxidative metabolism (confounding outcomes take place of certainties). Pharmacol. Toxicol., 2001, 89(5), 217-224.
[http://dx.doi.org/10.1034/j.1600-0773.2001.d01-151.x] [PMID: 11881974]
Fornai, F.; Giorgi, F.S.; Bassi, L.; Ferrucci, M.; Alessandrì, M.G.; Corsini, G.U. Modulation of dihydroxyphenylacetaldehyde extracellular levels in vivo in the rat striatum after different kinds of pharmacological treatment. Brain Res., 2000, 861(1), 126-134.
[http://dx.doi.org/10.1016/S0006-8993(00)02054-0] [PMID: 10751572]
Marchitti, S.A.; Deitrich, R.A.; Vasiliou, V. Neurotoxicity and metabolism of the catecholamine-derived 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde: the role of aldehyde dehydrogenase. Pharmacol. Rev., 2007, 59(2), 125-150.
[http://dx.doi.org/10.1124/pr.59.2.1] [PMID: 17379813]
Vianello, R.; Domene, C.; Mavri, J. The Use of Multiscale Molecular Simulations in Understanding a Relationship between the Structure and Function of Biological Systems of the Brain: The Application to Monoamine Oxidase Enzymes. Front. Neurosci., 2016, 10, 327.
[http://dx.doi.org/10.3389/fnins.2016.00327] [PMID: 27471444]
Götz, M.E.; Freyberger, A.; Riederer, P. Oxidative stress: a role in the pathogenesis of Parkinson’s disease. J. Neural Transm. Suppl., 1990, 29, 241-249.
[http://dx.doi.org/10.1007/978-3-7091-9050-0_23] [PMID: 2193108]
Youdim, M. B.; Bakhle, Y. S. Monoamine oxidase: isoforms and inhibitors in Parkinson’s disease and depressive illness., Br J Pharmacol, 2006, 147(Suppl 1), S287-96.147.
Grünblatt, E.; Mandel, S.; Jacob-Hirsch, J.; Zeligson, S.; Amariglo, N.; Rechavi, G.; Li, J.; Ravid, R.; Roggendorf, W.; Riederer, P.; Youdim, M.B. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J. Neural Transm. (Vienna), 2004, 111(12), 1543-1573.
[http://dx.doi.org/10.1007/s00702-004-0212-1] [PMID: 15455214]
Chiba, K.; Trevor, A.; Castagnoli, N., Jr Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem. Biophys. Res. Commun., 1984, 120(2), 574-578.
[http://dx.doi.org/10.1016/0006-291X(84)91293-2] [PMID: 6428396]
Langston, J.W.; Ballard, P.; Tetrud, J.W.; Irwin, I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science, 1983, 219(4587), 979-980.
[http://dx.doi.org/10.1126/science.6823561] [PMID: 6823561]
Singh, B.; Pandey, S.; Yadav, S.K.; Verma, R.; Singh, S.P.; Mahdi, A.A. Role of ethanolic extract of Bacopa monnieri against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice model via inhibition of apoptotic pathways of dopaminergic neurons. Brain Res. Bull., 2017, 135, 120-128.
[http://dx.doi.org/10.1016/j.brainresbull.2017.10.007] [PMID: 29032054]
Chen, J.F.; Steyn, S.; Staal, R.; Petzer, J.P.; Xu, K.; Van Der Schyf, C.J.; Castagnoli, K.; Sonsalla, P.K.; Castagnoli, N., Jr; Schwarzschild, M.A. 8-(3-Chlorostyryl)caffeine may attenuate MPTP neurotoxicity through dual actions of monoamine oxidase inhibition and A2A receptor antagonism. J. Biol. Chem., 2002, 277(39), 36040-36044.
[http://dx.doi.org/10.1074/jbc.M206830200] [PMID: 12130655]
Palacios, N.; Gao, X.; McCullough, M.L.; Schwarzschild, M.A.; Shah, R.; Gapstur, S.; Ascherio, A. Caffeine and risk of Parkinson’s disease in a large cohort of men and women. Mov. Disord., 2012, 27(10), 1276-1282.
[http://dx.doi.org/10.1002/mds.25076] [PMID: 22927157]
Rivara, S.; Piersanti, G.; Bartoccini, F.; Diamantini, G.; Pala, D.; Riccioni, T.; Stasi, M.A.; Cabri, W.; Borsini, F.; Mor, M.; Tarzia, G.; Minetti, P. Synthesis of (E)-8-(3-chlorostyryl)caffeine analogues leading to 9-deazaxanthine derivatives as dual A(2A) antagonists/MAO-B inhibitors. J. Med. Chem., 2013, 56(3), 1247-1261.
[http://dx.doi.org/10.1021/jm301686s] [PMID: 23281824]
Singh, K.; Singh, S.; Singhal, N.K.; Sharma, A.; Parmar, D.; Singh, M.P. Nicotine- and caffeine-mediated changes in gene expression patterns of MPTP-lesioned mouse striatum: Implications in neuroprotection mechanism. Chem. Biol. Interact., 2010, 185(2), 81-93.
[http://dx.doi.org/10.1016/j.cbi.2010.03.015] [PMID: 20230807]
Machado-Filho, J.A.; Correia, A.O.; Montenegro, A.B.; Nobre, M.E.; Cerqueira, G.S.; Neves, K.R.; Naffah-Mazzacoratti, Mda.G.; Cavalheiro, E.A.; de Castro Brito, G.A.; de Barros Viana, G.S. Caffeine neuroprotective effects on 6-OHDA-lesioned rats are mediated by several factors, including pro-inflammatory cytokines and histone deacetylase inhibitions. Behav. Brain Res., 2014, 264, 116-125.
[http://dx.doi.org/10.1016/j.bbr.2014.01.051] [PMID: 24525422]
Khadrawy, Y.A.; Salem, A.M.; El-Shamy, K.A.; Ahmed, E.K.; Fadl, N.N.; Hosny, E.N. Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson’s Disease Induced by Rotenone. J. Diet. Suppl., 2017, 14(5), 553-572.
[http://dx.doi.org/10.1080/19390211.2016.1275916] [PMID: 28301304]
Sonsalla, P.K.; Wong, L.Y.; Harris, S.L.; Richardson, J.R.; Khobahy, I.; Li, W.; Gadad, B.S.; German, D.C. Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson’s disease. Exp. Neurol., 2012, 234(2), 482-487.
[http://dx.doi.org/10.1016/j.expneurol.2012.01.022] [PMID: 22309831]
Yadav, S.; Gupta, S.P.; Srivastava, G.; Srivastava, P.K.; Singh, M.P. Role of secondary mediators in caffeine-mediated neuroprotection in maneb- and paraquat-induced Parkinson’s disease phenotype in the mouse. Neurochem. Res., 2012, 37(4), 875-884.
[http://dx.doi.org/10.1007/s11064-011-0682-0] [PMID: 22201039]
Kaster, M.P.; Machado, N.J.; Silva, H.B.; Nunes, A.; Ardais, A.P.; Santana, M.; Baqi, Y.; Müller, C.E.; Rodrigues, A.L.; Porciúncula, L.O.; Chen, J.F.; Tomé, Â.R.; Agostinho, P.; Canas, P.M.; Cunha, R.A. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress. Proc. Natl. Acad. Sci. USA, 2015, 112(25), 7833-7838.
[http://dx.doi.org/10.1073/pnas.1423088112] [PMID: 26056314]
Essayan, D.M. Cyclic nucleotide phosphodiesterases. J. Allergy Clin. Immunol., 2001, 108(5), 671-680.
[http://dx.doi.org/10.1067/mai.2001.119555] [PMID: 11692087]
Daly, J.W.; Jacobson, K.A.; Ukena, D. Adenosine receptors: development of selective agonists and antagonists. Prog. Clin. Biol. Res., 1987, 230, 41-63.
[PMID: 3588607]
Monteiro, J.P.; Alves, M.G.; Oliveira, P.F.; Silva, B.M. Structure-Bioactivity Relationships of Methylxanthines: Trying to Make Sense of All the Promises and the Drawbacks. Molecules, 2016, 21(8)E974
[http://dx.doi.org/10.3390/molecules21080974] [PMID: 27472311]
Garrett, B.E.; Griffiths, R.R. The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol. Biochem. Behav., 1997, 57(3), 533-541.
[http://dx.doi.org/10.1016/S0091-3057(96)00435-2] [PMID: 9218278]
Mitchell, D.C.; Knight, C.A.; Hockenberry, J.; Teplansky, R.; Hartman, T.J. Beverage caffeine intakes in the U.S. Food Chem. Toxicol., 2014, 63, 136-142.
[http://dx.doi.org/10.1016/j.fct.2013.10.042] [PMID: 24189158]
McCall, A.L.; Millington, W.R.; Wurtman, R.J. Blood-brain barrier transport of caffeine: dose-related restriction of adenine transport. Life Sci., 1982, 31(24), 2709-2715.
[http://dx.doi.org/10.1016/0024-3205(82)90715-9] [PMID: 7154859]
Smith, A. Effects of caffeine on human behavior. Food Chem. Toxicol., 2002, 40(9), 1243-1255.
[http://dx.doi.org/10.1016/S0278-6915(02)00096-0] [PMID: 12204388]
Aoyama, K.; Matsumura, N.; Watabe, M.; Wang, F.; Kikuchi-Utsumi, K.; Nakaki, T. Caffeine and uric acid mediate glutathione synthesis for neuroprotection. Neuroscience, 2011, 181, 206-215.
[http://dx.doi.org/10.1016/j.neuroscience.2011.02.047] [PMID: 21371533]
Ross, G.W.; Petrovitch, H. Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson’s disease. Drugs Aging, 2001, 18(11), 797-806.
[http://dx.doi.org/10.2165/00002512-200118110-00001] [PMID: 11772120]
Ascherio, A.; Zhang, S.M.; Hernán, M.A.; Kawachi, I.; Colditz, G.A.; Speizer, F.E.; Willett, W.C. Prospective study of caffeine consumption and risk of Parkinson’s disease in men and women. Ann. Neurol., 2001, 50(1), 56-63.
[http://dx.doi.org/10.1002/ana.1052] [PMID: 11456310]
Costa, J.; Lunet, N.; Santos, C.; Santos, J.; Vaz-Carneiro, A. Caffeine exposure and the risk of Parkinson’s disease: a systematic review and meta-analysis of observational studies. J. Alzheimers Dis., 2010, 20(Suppl. 1), S221-S238.
[http://dx.doi.org/10.3233/JAD-2010-091525] [PMID: 20182023]
Altman, R.D.; Lang, A.E.; Postuma, R.B. Caffeine in Parkinson’s disease: a pilot open-label, dose-escalation study. Mov. Disord., 2011, 26(13), 2427-2431.
[http://dx.doi.org/10.1002/mds.23873] [PMID: 21953603]
Liu, R.; Guo, X.; Park, Y.; Huang, X.; Sinha, R.; Freedman, N.D.; Hollenbeck, A.R.; Blair, A.; Chen, H. Caffeine intake, smoking, and risk of Parkinson disease in men and women. Am. J. Epidemiol., 2012, 175(11), 1200-1207.
[http://dx.doi.org/10.1093/aje/kwr451] [PMID: 22505763]
Ascherio, A.; Schwarzschild, M.A. The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol., 2016, 15(12), 1257-1272.
[http://dx.doi.org/10.1016/S1474-4422(16)30230-7] [PMID: 27751556]
Kolahdouzan, M.; Hamadeh, M.J. The neuroprotective effects of caffeine in neurodegenerative diseases. CNS Neurosci. Ther., 2017, 23(4), 272-290.
[http://dx.doi.org/10.1111/cns.12684] [PMID: 28317317]
Traube, W. Der synthetische Aufbau der Harnsäure, des Xanthins, Theobromins, Theophyllins und Caffeïns aus der Cyanessigsäure. Chem. Ber., 1900, 33, 3035-3056.
Hu, S.; Nian, S.; Qin, K.; Xiao, T.; Li, L.; Qi, X.; Ye, F.; Liang, G.; Hu, G.; He, J.; Yu, Y.; Song, B. Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B. Chem. Pharm. Bull. (Tokyo), 2012, 60(3), 385-390.
[http://dx.doi.org/10.1248/cpb.60.385] [PMID: 22382421]
Strydom, B.; Bergh, J.J.; Petzer, J.P. 8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase. Eur. J. Med. Chem., 2011, 46(8), 3474-3485.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.014] [PMID: 21621312]
Mostert, S.; Mentz, W.; Petzer, A.; Bergh, J.J.; Petzer, J.P. Inhibition of monoamine oxidase by 8-[(phenylethyl)sulfanyl]caffeine analogues. Bioorg. Med. Chem., 2012, 20(24), 7040-7050.
[http://dx.doi.org/10.1016/j.bmc.2012.10.005] [PMID: 23122934]

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