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CNS Neuroprotection pp 177–208Cite as

Adenosine-Based Approaches to the Treatment of Neurodegenerative Disease

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 155))

Abstract

Adenosine is arguably the prototypic “neuromodulator” and has been described as the brain’s natural anticonvulsant (Druganow 1986) and neuroprotective agent (Rudolphi et al. 1992). The ability of adenosine to inhibit neuronal activity has been repeatedly demonstrated over the years in many kinds of in vitro and in vivo experiments. The stimulant effects of the adenosine receptor antagonists, caffeine and theophylline, are due to a reversal of adenosine’s inhibitory tone in the central nervous system (CNS), a phenomenon that has been experienced by virtually every human being on the planet! Because of these well-documented effects on the animal and human CNS, efforts have been made over the past several decades to harness the neuronal depressant activities of adenosine for therapeutic advantage, including the treatment of neurodegenerative diseases. Despite these efforts, no drugs are currently in clinical use for CNS disorders that act specifically on the adenosine system. Perhaps the major reason for this has been concerns over the side effects which are observed when adenosine receptors are activated. The principle worries are the general sedative effects and alterations in cardiovascular function caused by agents which activate adenosine receptors, since adenosine also has potent depressant effects on the heart and is an effective vasodilator. However, some recent strategies have been devised either to minimize or avoid these potential side-effect concerns.

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References

  • Abbracchio MP, Brambilla R, Ceruti S, Kim HO, von Lubitz DK, Jacobson KA, Cattabeni F (1995) G protein-dependent activation of phospholipase C by adenosine A3 receptors in rat brain. Mol Pharmacol 48:1038–1045

    PubMed  CAS  Google Scholar 

  • Andine P, Rudolphi KA, Fredholm BB, Hagberg H (1990) Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia. Br J Pharmacol 100:814–818

    PubMed  CAS  Google Scholar 

  • Arvin B, Neville LF, Roberts PJ (1988) 2-Chloroadenosine prevents kainic acid-induced toxicity in rat striatum. Neurosci Lett 93:336–340

    PubMed  CAS  Google Scholar 

  • Ashton D, De Prins E, Willems R, Van Belle H, Wauquier A (1988) Anticonvulsant action of the nucleoside transport inhibitor, soluflazine, on synaptic and nonsynaptic epileptogenesis in the guinea-pig hippocampus. Epilepsy Res 2:65–71

    PubMed  CAS  Google Scholar 

  • Ashton D, Willems R, De Prins E, Van Belle H, Wauquier A (1987) The nucleoside-transport inhibitor soluflazine (R 64 719) increases the effects of adenosine in the guinea-pig hippocampal slice and is antagonized by adenosine deaminase. Eur J Pharmacol 142:403–408

    PubMed  CAS  Google Scholar 

  • Bailarin M, Herrera-Marschitz M, Casas M, Ungerstedt U (1987) Striatal adenosine levels measured “in vivo” by microdialysis in rats with unilateral dopamine denervation. Neurosci Lett 83:338–344

    Google Scholar 

  • Bari F, Louis TM, Busija DW (1998) Effects of ischemia on cerebral arteriolar dilation to arterial hypoxia in piglets. Stroke 29:222–227

    PubMed  CAS  Google Scholar 

  • Barth A, Newell DW, Nguyen LB, Winn HR, Wender R, Meno JR, Janigro D (1997) Neurotoxicity in organotypic hippocampal slices mediated by adenosine analogues and nitric oxide. Brain Res 762:79–88

    PubMed  CAS  Google Scholar 

  • Bell MJ, Kochanek PM, Cardilo JA, Mi Z, Schiding JK, Wisniewski SR, Clark RS, Dixon CE, Marion DW, Jackson E (1998) Interstitial adenosine, inosine, and hypoxanthine are increased after experimental traumatic brain injury in the rat. J Neurotrauma 15:163–170

    PubMed  CAS  Google Scholar 

  • Blandini F, Porter RH, Greenamyre JT (1996) Glutamate and Parkinson’s disease. Mol Neurobiol 12:73–94

    PubMed  CAS  Google Scholar 

  • Boissard CG, Gribkoff VK (1993) The effects of the adenosine reuptake inhibitor soluflazine on synaptic potentials and population hypoxic depolarizations in area CA1 of rat hippocampus in vitro. Neuropharmacology 32:149–155

    PubMed  CAS  Google Scholar 

  • Bona E, Aden U, Gilland E, Fredholm BB, Hagberg H (1997) Neonatal cerebral hypoxia-ischemia: the effect of adenosine receptor antagonists. Neuropharmacology 36:1327–1338

    PubMed  CAS  Google Scholar 

  • Britton DR, Mikusa J, Lee CH, Jarvis MF, Williams M, Kowaluk EA (1999) Site and event specific increase of striatal adenosine release by adenosine kinase inhibition in rats. Neurosci Lett 266:93–96

    PubMed  CAS  Google Scholar 

  • Brundege JM, Dunwiddie TV (1998) Metabolic regulation of endogenous adenosine release from single neurons. NeuroReport 9:3007–3011

    PubMed  CAS  Google Scholar 

  • Brundege JM, Dunwiddie TV (1997) Role of adenosine as a modulator of synaptic activity in the central nervous system. Advances in Pharmacology 39:353–391

    PubMed  CAS  Google Scholar 

  • Brundege JM, Dunwiddie TV (1996) Modulation of excitatory synaptic transmission by adenosine released from single hippocampal pyramidal neurons. J Neuroscience 16:5603–5612

    CAS  Google Scholar 

  • Bruns RF, Fergus JH (1990) Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. Mol Pharmacol 38:939–949

    PubMed  CAS  Google Scholar 

  • Bruns RF, Fergus JH, Coughenour LL, Courtland GG, Pugsley TA, Dodd JH, Tinney FJ (1990) Structure-activity relationships for enhancement of adenosine A1 receptor binding by 2-amino-3-benzoylthiophenes. Mol Pharmacol 38:950–958

    PubMed  CAS  Google Scholar 

  • Clark RS, Cardilo JA, Kochanek PM, Obrist WD, Jackson EK, Mi Z, Wisniewski SR, Bell MJ (1997) Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans. Neurosurgery 41:1284–1292

    PubMed  CAS  Google Scholar 

  • Cao X, Phillis JW (1995) Adenosine A1 receptor enhancer, PD 81,723, and cerebral ischemia/reperfusion injury in the gerbil. Gen Pharmacol 26:1545–1548

    PubMed  CAS  Google Scholar 

  • Croning MD, Zetterstrom TS, Grahame-Smith DG, Newberry NR (1995) Action of adenosine receptor antagonists on hypoxia-induced effects in the rat hippocampus in vitro. Br J Pharmacol 116:2113–2119

    PubMed  CAS  Google Scholar 

  • Daval JL, Nicolas F (1994) Opposite effects of cyclohexyladenosine and theophylline on hypoxic damage in cultured neurons. Neurosci Lett 175:114–116

    PubMed  CAS  Google Scholar 

  • Duval JL, Von Lubitz DK, Deckert J, Redond DJ, Marangos PJ (1989) Protective effect of cyclohexyladenosine on adenosine A1-receptors, guanine nucleotide and forskolin binding sites following transient brain ischemia: a quantitative autoradiographic study. Brain Res 491:212–226

    Google Scholar 

  • DeLeo J, Schubert P, Kreutzberg GW (1988) Propentoflline (HWA 285) protects hippocampal neurons of Mongolian gerbils against ischemic damage in the presence of an adenosine antagonist. Neurosci Lett 84:307–311

    Google Scholar 

  • Delle Donne KT, Sonsalla PK (1994) Protection against methamphetamine-induced neurotoxicity to neostriatal dopaminergic neurons by adenosine receptor activation. J Pharmacol Exp Ther 271:1320–1326

    Google Scholar 

  • Dietrich WD, Miller LP, Prado R, Dewanjee S, Alex N, Dewanjee MK, Gruber H (1995) Acadesine reduces indium-labeled platelet deposition after photothrombosis of the common carotid artery in rats. Stroke 26:111–116

    PubMed  CAS  Google Scholar 

  • Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:141–148

    Google Scholar 

  • Dolphin AC, Archer ER (1983) An adenosine agonist inhibits and a cyclic AMP analog enhances the release of glutamate but not GABA from slices of rat dentate gyrus. Neurosci Lett 43:49–54

    PubMed  CAS  Google Scholar 

  • Doolette DJ (1997) Mechanism of adenosine accumulation in the hippocampal slice during energy deprivation. Neurochem Int 30:211–223

    PubMed  CAS  Google Scholar 

  • Doolette DJ, Kerr, DI (1995) Hyperexcitability in CA1 of the rat hippocampal slice following hypoxia or adenosine. Brain Res 677:127–137

    PubMed  CAS  Google Scholar 

  • Dragunow M, Goddard GV, Laverty R (1985) Is adenosine an endogenous anticonvulsant? Epilepsia 26:480–487

    PubMed  CAS  Google Scholar 

  • Dunwiddie TV, Diao L, Kim HO, Jiang JL, Jacobson KA (1997a) Activation of hippocampal adenosine A3 receptors produces a desensitization of A1 receptor-mediated responses in rat hippocampus. J Neuroscience 17:607–614

    CAS  Google Scholar 

  • Dunwiddie TV, Diao L, Proctor WR (1997b) Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J Neuroscience 17:7673–7682

    CAS  Google Scholar 

  • During MJ, Spencer DD (1992) Adenosine: a potential mediator of seizure arrest and postictal refractoriness. Ann Neurol 32:618–624

    PubMed  CAS  Google Scholar 

  • Dux E, Fastbom J, Ungerstedt U, Rudolphi K, Fredholm BB (1990) Protective effect of adenosine and a novel xanthine derivative propentofyline on the cell damage after bilateral carotid occlusion in the gerbil hippocampus. Brain Res 516:248–256

    PubMed  CAS  Google Scholar 

  • Evans MC, Swan JH, Meldrum BS (1987) An adenosine analogue, 2-chloroadenosine, protects against long term development of ischaemic cell loss in the rat hippocampus. Neuroscience Lett 83:287–292

    CAS  Google Scholar 

  • Fern R, Waxman SG, Ransom BR (1994) Modulation of anoxic injury in CNS white matter by adenosine and interaction between adenosine and GABA. J Neurophysiol 72:2609–2616

    PubMed  CAS  Google Scholar 

  • Ferré S, Fredholm BB, Morelli M, Popoli P, Fuxe K (1997) Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. TINS 20:482–487

    PubMed  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Finn SF, Swartz KJ, Beal MF (1991) 2-Chloroadenosine attenuates NMDA, kainate, and quisqualate toxicity. Neurosci Lett 126:191–194

    PubMed  CAS  Google Scholar 

  • Firestein GS, Bullough DA, Erion MD, Jimenez R, Ramirez-Weinhouse M, Barankiewicz J, Smith CW, Gruber HE, Mullane KM (1995) Inhibition of neutrophil adhesion by adenosine and an adenosine kinase inhibitor. The role of selectins. J Immunol 154:326–334

    PubMed  CAS  Google Scholar 

  • Fuxe K, Ungerstedt U (1974) Action of caffeine and theophyllamine on supersensitive dopamine receptors: considerable enhancement of receptor response to treatment with DOPA and dopamine receptor agonists. Med Bio 52:48–54

    CAS  Google Scholar 

  • Gao Y, Phillis JW (1994) CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil. Life Sci 55: PL61–PL65

    Google Scholar 

  • Gidday JM, Fitzgibbons JC, Shah AR, Kraujalis MJ, Park TS (1995) Reduction in cerebral ischemic injury in the newborn rat by potentiation of endogenous adenosine. Pediatr Res 38:306–311

    PubMed  CAS  Google Scholar 

  • Goldberg MP, Moyer H, Weiss JH, Choi DW (1988) Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro. Neuroscience Lett 89:323–327

    CAS  Google Scholar 

  • Greenamyre JT, Eller RV, Zhang Z, Ovadia A, Kurlan R, Gash DM (1994) Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson’s disease. Ann Neurol 35:655–661

    PubMed  CAS  Google Scholar 

  • Greene RW, Haas HL (1991) The electrophysiology of adenosine in the mammalian central nervous system. Prog Neurobiol 36:329–341

    PubMed  CAS  Google Scholar 

  • Gribkoff VK, Bauman LA, VanderMaelen CP (1990) The adenosine antagonist 8-cyclopentyltheophylline reduces the depression of hippocampal neuronal responses during hypoxia. Brain Res 512:353–357

    PubMed  CAS  Google Scholar 

  • Griffith DA, Conant AR, Jarvis SM (1990) Differential inhibition of nucleoside transport systems in mammalian cells by a new series of compounds related to lidoflazine and mioflazine. Biochem Pharmacol 40:2297–303

    PubMed  CAS  Google Scholar 

  • Griffiths M, Beaumont N, Yao SYM, Sundaram M, Boumah CE, Davies A, Kwong FYP, Coe I, Cass CE, Young JD, Baldwin SA (1997a) Cloning of a human nucleoside transporter implicated in cellular uptake of adenosine and chemotherapeutic drugs. Nature Medicine 3:89–93

    PubMed  CAS  Google Scholar 

  • Griffiths M, Yao SY, Abidi F, Phillips SE, Cass CE, Young JD, Baldwin SA (1997b) Molecular cloning and characterization of a nitrobenzylthioinosine-insensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem J 328:739–743

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Gruber HE, Hoffer ME, McAllister DR, Laikind PK, Lane TA, Schmid-Schoenbein GW, Engler RL (1989) Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury. Circulation 80:1400–1411

    PubMed  CAS  Google Scholar 

  • Guieu R, Dussol B, Halimi G, Bechis G, Sampieri F, Berland Y, Sampol J, Couraud F, Rochat H (1998) Adenosine and the nervous system: pharmacological data and therapeutic perspectives. Gen Pharmacol 31:553–561

    PubMed  CAS  Google Scholar 

  • Halle JN, Kasper CE, Gidday JM, Koos BJ (1997) Enhancing adenosine A1 receptor binding reduces hypoxic-ischemic brain injury in newborn rats. Brain Res 759:309–312

    PubMed  CAS  Google Scholar 

  • Hauber W, Nagel J, Sauer R, Müller CE (1998) Motor effects induced by a blockade of adenosine A2A receptors in the caudate-putamen. NeuroReport 9:1803–1806

    PubMed  CAS  Google Scholar 

  • Headrick JP, Bendali MR, Faden AI, Vink R (1994) Dissociation of adenosine levels from bioenergetic state in experimental brain trauma: potential role in secondary injury. J Cereb Blood Flow Metab 14:853–861

    PubMed  CAS  Google Scholar 

  • Heurteaux C, Lauritzen I, Widmann C, Lazdunski M (1995) Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci USA 92:4666–4670

    PubMed  CAS  Google Scholar 

  • Huston JP, Haas HL, Boix F, Pfister M, Decking U, Schrader J, Schwarting RK (1996) Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats. Neuroscience 73:99–107

    PubMed  CAS  Google Scholar 

  • Jacobson KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 19:184–191

    PubMed  CAS  Google Scholar 

  • Jacobson KA, van Galen PJ, Williams M (1992) Adenosine receptors: pharmacology, structure-activity relationships, and therapeutic potential. J Med Chem 35:407–422

    PubMed  CAS  Google Scholar 

  • Janusz CA, Berman RF (1993) The adenosine binding enhancer, PD 81,723, inhibits epileptiform bursting in the hippocampal brain slice. Brain Res 619:131–136

    PubMed  CAS  Google Scholar 

  • Janusz CA, Bruns RF, Berman RF (1991) Functional activity of the adenosine binding enhancer, PD 81,723, in the in vitro hippocampal slice. Brain Res 567:181–187

    PubMed  CAS  Google Scholar 

  • Jiang N, Kowaluk EA, Lee CH, Mazdiyasni H, Chopp M (1997) Adenosine kinase inhibition protects brain against transient focal ischemia in rats. Eur J Pharmacol 320:131–137

    PubMed  CAS  Google Scholar 

  • Jo Y-H, Schlicter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nature Neuroscience 2:241

    PubMed  CAS  Google Scholar 

  • Johnson MP, McCarty DR, Chmielewski PA (1998) Temporal dependent neuroprotection with propentofylline (HWA 285) in a temporary focal ischemia model. Eur J Pharmacol 356:151–157

    Google Scholar 

  • Jones PA, Smith RA, Stone TW (1998) Protection against hippocampal kainite excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800:328–335

    PubMed  CAS  Google Scholar 

  • Jones KW, Hammond JR (1995) Characterization of nucleoside transport activity in rabbit cortical synaptosomes. Can J Physiol Pharmacol 83:1733–1741

    Google Scholar 

  • Kanda T, Jackson MJ, Smith LA, Pearce RKB, Nakamura J, Kase H, Kuwana Y, Jenner P (1998a) Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Annals of Neurology 43:508–513

    Google Scholar 

  • Kanda T, Tashiro T, Kuwana Y, Jenner P (1998b) Adenosne A2A receptors modify motor function in MPTP-treated common marmosets. NeuroReport 9:2857–2860

    PubMed  CAS  Google Scholar 

  • Katchman AN, Hershkowitz N (1993) Adenosine antagonists prevent hypoxia-induced depression of excitatory but not inhibitory synaptic currents. Neurosci Lett 159:123–126

    PubMed  CAS  Google Scholar 

  • Kawahara N, Ide T, Saito N, Kawai K, Kirino T (1998) Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor. J Cereb Blood Flow Metab 18:472–475

    PubMed  CAS  Google Scholar 

  • Kirk IP, Richardson PJ (1994) Adenosine A2a receptor-mediated modulation of striatal [3H]GABA and [3H]acetylcholine release. J Neurochem 62:960–966

    PubMed  CAS  Google Scholar 

  • Kittner B, Rossner M, Rothr M (1997) Clinical trials in dementia with propentofylline. Ann NY Acad Sci 826:307–316

    PubMed  CAS  Google Scholar 

  • Knutsen LJS, Murray TF (1997) Adenosine and ATP in epilepsy. In: Jacobson KA, Jarvis MF (eds) Purinergic Approaches in Experimental Therapeutics, pp 423–447, Wiley-Liss, New York

    Google Scholar 

  • Kochanek PM, Clark RS, Obrist WD, Cardilo JA, Jackson EK, Mi Z, Wisniewski SR, Bell MJ, Marion DW (1997) The role of adenosine during the period of delayed cerebral swelling after severe traumatic brain injury in humans. Acta Neurochir Suppl (Wien) 70:109–111

    CAS  Google Scholar 

  • Kurokawa M, Kirk IP, Kirkpatrick KA, Kase H, Richardson PJ (1994) Inhibition by KF17837 of adenosine A2A receptor-mediated modulation of striatal GABA and Ach release. Br J Pharmacol 113:43–48

    PubMed  CAS  Google Scholar 

  • Lau YS, Mouradian MM (1993) Protection against acute MPTP-induced dopamine depletion in mice by adenosine A1 agonist. J Neurochem 60:768–771

    PubMed  CAS  Google Scholar 

  • Lekieffre D, Callebert J, Plotkine M, Allix M, Boulu RG (1991) Enhancement of endogenous excitatory amino acids by theophylline does not modify the behavioral and histological consequences of forebrain ischemia. Brain Res 565:353–357

    PubMed  CAS  Google Scholar 

  • Lin Y, Phillis JW (1992) Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat. Brain Res 571:272–280

    PubMed  CAS  Google Scholar 

  • Lobner D, Choi DW (1994) Dipyridamole increases oxygen-glucose deprivation-induced injury in cortical cell culture. Stroke 25:2085–2089;

    PubMed  CAS  Google Scholar 

  • discussion 2089–2090 Logan M, Sweeney MI (1997) Adenosine A1 receptor activation preferentially protects cultured cerebellar neurons versus astrocytes against hypoxia-induced death. Mol Chem Neuropathol 31:119–133

    PubMed  CAS  Google Scholar 

  • Lynch JJ 3rd, Alexander KM, Jarvis MF, Kowaluk EA (1998) Inhibition of adenosine kinase during oxygen-glucose deprivation in rat cortical neuronal cultures. Neurosci Lett 252:207–210

    PubMed  CAS  Google Scholar 

  • Macek TA, Schaffhauser H, Conn PJ (1998) Protein kinase C and A3 adenosine receptor activation inhibit presynaptic metabotropic glutamate receptor (mGluR) function and uncouple mGluRs from GTP-binding proteins. J Neurosci 18:6138–6146

    PubMed  CAS  Google Scholar 

  • MacGregor DG, Graham DI, Jones PA, Stone TW (1998) Protection by an adenosine analogue against kainate-induced extrahippocampal neuropathology. Gen Pharmacol 31:233–238

    PubMed  CAS  Google Scholar 

  • MacGregor DG, Jones PA, Maxwell WL, Graham DI, Stone TW (1996) Prevention by a purine analogue of kainate-induced neuropathology in rat hippocampus. Brain Res 725:115–120

    PubMed  CAS  Google Scholar 

  • Manzoni OJ, Manabe T, Nicoli RA (1994) Release of adenosine by activation of NMDA receptors in the hippocampus. Science 265:2098–2101

    PubMed  CAS  Google Scholar 

  • Marston HM, Finlayson K, Maemoto T, Olverman HJ, Akahane, A, Sharkey J, Butcher SP (1998) Pharmacological characterization of a simple behavioral response mediated selectively by central adenosine A1 receptors, using in vivo and in vitro techniques. J Pharmacology Exp Therapeutics 285:1023–1030

    CAS  Google Scholar 

  • Martinez-Mir MI, Probst A, Palacios JM (1991) Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease. Neuroscience 42:697–706

    PubMed  CAS  Google Scholar 

  • Masino SA, Dunwiddie TV (1999) Temperature-dependent modulation of excitatory transmission in hippocampal slices is mediated by Extracellular adenosine. J Neuroscience 19:1932–1939

    CAS  Google Scholar 

  • Matsumoto K, Graf R, Rosner G, Taguchi J, Heiss WD (1993) Elevation of neuroactive substances in the cortex of cats during prolonged focal ischemia. J Cereb Blood Flow Metab 13:586–594

    PubMed  CAS  Google Scholar 

  • Meno JR, Ngai AC, Winn HR (1993) Changes in pial arteriolar diameter and CSF adenosine concentrations during hypoxia. J Cerebral Blood Flow and Metabolism 13:214–220

    CAS  Google Scholar 

  • Michel PP, Marien M, Ruberg M, Colpaert F, Agid Y (1999) Adenosine prevents the death of mesencephalic dopaminergic neurons by a mechanism that involves astrocytes. J Neurochem 72:2074–2082

    PubMed  CAS  Google Scholar 

  • Miller LP (1999) Adenosine in ischemic brain injury. In Stroke therapy, basic, preclinical directions, Ed Leonard P. Miller, Wiley-Liss, Inc.

    Google Scholar 

  • Miller LP, Jelovich LA, Yao L, DaRe J, Ugarkar B, Foster AC (1996) Pre- and peristroke treatment with the adenosine kinase inhibitor, 5′-deoxyiodotubercidin, significantly reduces infarct volume after temporary occlusion of the middle cerebral artery in rats. Neurosci Lett 220:73–76

    PubMed  CAS  Google Scholar 

  • Miller LP, Chiang PC, Carriedo S, Metzner K, Foster AC (1994) The adenosine regulating agent, GP-1–668, reduces infarct volume and neurological deficits in a rat model of focal stroke with reperfusion. Abs. Stroke Council 19th International Joint Converence on Stroke and Cerebral Circulation, February 17–19, 1994, San Diego, CA USA, p 21

    Google Scholar 

  • Miller LP, Hsu C (1992) Therapeutic potential for adenosine receptor activation in ischemic brain injury. J Neurotrauma 9 [Suppl 2]:S563–S577

    Google Scholar 

  • Mitchell JB, Lupica CR, Dunwidde TV (1993) Activity-dependent release of endogenous adenosine modulates synaptic responses in the rat hippocampus. J Neurosci 13:3439–3447

    PubMed  CAS  Google Scholar 

  • Mitchell HL, Frisella WA, Brooker RW, Yoon KW (1995) Attenuation of traumatic cell death by an adenosine A1 agonist in rat hippocampal cells. Neurosurgery 36:1003–1007; discussion 1007–1008

    PubMed  CAS  Google Scholar 

  • Mizumura T, Auchampach JA, Linden J, Bruns RF, Gross GJ (1996) PD 81,723, an allosteric enhancer of the A1 adenosine receptor, lowers the threshold for ischemic preconditioning in dogs. Circ Res 79:415–423

    PubMed  CAS  Google Scholar 

  • Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (1998) Blockade of adenosine A2A receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport 9:3955–3959

    PubMed  CAS  Google Scholar 

  • Mori A, Shindou T, Ichimura M, Nonaka H, Kase H (1996) The role of adenosine A2a receptors in regulating GABAergic synaptic transmission in striatal medium spiny neurons. J Neurosci 16:605–611

    PubMed  CAS  Google Scholar 

  • Musser B, Mudumbi RV, Liu J, Olson RD, Vestal RE (1999) Adenosine A1 receptor-dependent and -independent effects of the allosteric enhancer PD 81,723. J Pharmacol Exp Ther 288:446–454

    PubMed  CAS  Google Scholar 

  • Nagata K, Ogawa T, Omosu M, Fujimoto K, Hayashi S (1985) In vitro and in vivo inhibitory effects of propentofylline on cyclic AMP phosphodiesterase activity. Arzneimittelforschung 35:1034–1036

    PubMed  CAS  Google Scholar 

  • Nilsson P, Hillered L, Ponten U, Ungerstedt U (1990) Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab 19:631–637

    Google Scholar 

  • O’Connor SD, Stojanovic M, Radulovacki M (1991) The effect of soluflazine on sleep in rats. Neuropharmacology 30:671–674

    PubMed  Google Scholar 

  • Ongini E, Adami M, Ferri C, Bertorelli R (1997) Adenosine A2A receptors and neuroprotection. Ann NY Acad Sci 825:30–48

    PubMed  CAS  Google Scholar 

  • Pak MA, Haas HL, Decking UK, Schrader J (1994) Inhibition of adenosine kinase increases endogenous adenosine and depresses neuronal activity in hippocampal slices. Neuropharmacology 33:1049–1053

    PubMed  CAS  Google Scholar 

  • Park CK, Rudolphi KA (1994) Antiischemic effects of propentofylline (HWA 285) against focal cerebral infarction in rats. Neurosci Lett 178:235–238

    PubMed  CAS  Google Scholar 

  • Perez-Pinzon MA, Mumford PL, Rosenthal M, Sick TJ (1996) Anoxic preconditioning in hippocampal slices: role of adenosine. Neuroscience 75:687–694

    PubMed  CAS  Google Scholar 

  • Phillis JW (1995) The effects of selective A1 and A2a adenosine receptor antagonists on cerebral ischemic injury in the gerbil. Brain Res 705:79–84

    PubMed  CAS  Google Scholar 

  • Phillis JW, Smith-Barbour M, Perkins LM, O’Regan MH (1994) Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex. Brain Res Bull 34:457–466

    PubMed  CAS  Google Scholar 

  • Phillis JW, Smith-Barbour M (1993) The adenosine kinase inhibitor, 5-iodotubercidin, is not protective against cerebral ischemic injury in the gerbil. Life Sci 53:497–502

    PubMed  CAS  Google Scholar 

  • Phillis JW, O’Regan MH (1989) Deoxycoformycin antagonizes ischemia-induced neuronal degeneration. Brain Res Bull 22:537–540

    PubMed  CAS  Google Scholar 

  • Phillis JW, O’Regan MH, Walter GA (1989) Effects of two nucleoside transport inhibitors, dipyridamole and soluflazine, on purine release from the rat cerebral cortex. Brain Res 481:309–316

    PubMed  CAS  Google Scholar 

  • Picano E, Abbracchio MP (1998) European stroke prevention study-2 results: serendipitous demonstration of neuroprotection induced by endogenous adenosine accumulation. TIPS 19:14–16

    PubMed  CAS  Google Scholar 

  • Pinard E, Riche D, Puiroud S, Seylaz J (1990) Theophylline reduces cerebral hyperaemia and enhances brain damage induced by seizures. Brain Res 511:303–309

    PubMed  CAS  Google Scholar 

  • Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW (1997) Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 276:1265–1268

    PubMed  CAS  Google Scholar 

  • Portas CM, Thakkar M, Rainnie DG, Greene RW, McCarley RW (1997) Role of adenosine in behavioral state modulation: a microdialysis study in the freely moving car. Neuroscience 79:225–235

    PubMed  CAS  Google Scholar 

  • Rainnie DG, Grunze HC, McCarley RW, Greene RW (1994) Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal. Science 263: 689–692

    PubMed  CAS  Google Scholar 

  • Richardson PJ, Kase H, Jenner PG (1997) Adenosine A2A receptor antagonists as new agents for the treatment of Parkinson’s disease. TIPS 17:338–344

    Google Scholar 

  • Rogler-Brown T, Agarwal RP, Parks RE Jr (1978) Tight binding inhibitors-VI. Interactions of deoxycoformycin and adenosine deaminase in intact human erythrocytes and sarcoma 180 cells. Biochem Pharmacol 27:2289–2296

    PubMed  CAS  Google Scholar 

  • Roussel S, Pinard E, Seylaz J (1991) Focal cerebral ischemia in chronic hypertension: no protection by R-phenylisopropyladenosine. Brain Res 545:171–174

    PubMed  CAS  Google Scholar 

  • Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB (1992) Neuroprotective role of adenosine in cerebral ischaemia. TIPS 13:439–445

    PubMed  CAS  Google Scholar 

  • Rudolphi KA, Keil M, Fastbom J, Fredholm BB (1989) Ischaemic damage in gerbil hippocampus is reduced following upregulation of adenosine (A1) receptors by caffeine treatment. Neurosci Lett 103:275–280

    PubMed  CAS  Google Scholar 

  • Rudolphi KA, Keil M, Hinze HJ (1987) Effect of theophylline on ischemically induced hippocampal damage in Mongolian gerbils: a behavioral and histopathological study. J Cereb Blood Flow Metab 7:74–81

    PubMed  CAS  Google Scholar 

  • Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991a) 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

    PubMed  CAS  Google Scholar 

  • Schiffmann SN, Libert F, Vassart G, Vanderhaeghen JJ (1991b) Distribution of adenosine A2 receptor mRNA in the human brain. Neurosci Lett 130:177–181

    PubMed  CAS  Google Scholar 

  • Schubert P, Ogata T, Miyazaki H, Marchini C, Ferroni S, Rudolphi K (1998) Pathological immuno-reactions of glial cells in Alzheimer’s disease and possible sites of interference. J Neural Transm Suppl 54:167–174

    PubMed  CAS  Google Scholar 

  • Schwarcz R, Ben-Ari Y (1986) Acids and epilepsy. Advances in Experimental Medicine and Biology, Vol. 203, Plennum Press, New York

    Google Scholar 

  • Sciotti VM, Van Wylen DG (1993) Increases in interstitial adenosine and cerebral blood flow with inhibition of adenosine kinase and adenosine deaminase. J Cereb Blood Flow Metab 13:201–207

    PubMed  CAS  Google Scholar 

  • Sciotti VM, Roche FM, Grabb MC, Van Wylen DG (1992) Adenosine receptor blockade augments interstitial fluid levels of excitatory amino acids during cerebral ischemia. J Cereb Blood Flow Metab 12:646–655

    PubMed  CAS  Google Scholar 

  • Seida M, Wagner HG, Vass K, Klatzo I (1988) Effect of aminophylline on postischemic edema and brain damage in cats. Stroke 10:1275–1282

    Google Scholar 

  • Sonsalla PK, Albers DS, Zeevalk GD (1998) Role of glutamate in neurodegeneration of dopamine neurons in several animal models of parkinsonism. Amino Acids 14:69–74

    PubMed  CAS  Google Scholar 

  • Sutherland GR, Peeling J, Lesiuk HJ, Brownstone RM, Rydzy M, Saunders JK, Geiger JD (1991) The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology. Neuroscience 42:171–182

    PubMed  CAS  Google Scholar 

  • Svenningsson P, Le Moine C, Aubert I, Burbaud P, Fredholm BB, Bloch B (1998) Cellular distribution of adenosine A2A receptor mRNA in the primate striatum. J Comp Neurol 399:229–240

    PubMed  CAS  Google Scholar 

  • Tatlisumak T, Takano K, Carana RA, Miller LP, Foster AC, Fisher M (1998) Delayed treatment with an adenosine kinase inhibitor, GP683, attenuates infarct size in rats with temporary middle cerebral artery occlusion. Stroke 29:1952–1958

    PubMed  CAS  Google Scholar 

  • Thompson SM, Haas HL, Gahwiler BH (1992) Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro. J Physiol (Lond) 451:347–363

    CAS  Google Scholar 

  • Thorn JA, Jarvis SM (1996) Adenosine Transporters. Gen Pharmac 27:613–620

    CAS  Google Scholar 

  • Turski WA, Cavalheiro EA, Ikonomidou C, Mello LE, Bortolotto ZA, Turski L (1985) Effects of aminophylline and 2-chloroadenosine on seizures produced by pilocarpine in rats: morphological and electroencephalographic correlates. Brain Res 361:309–323

    PubMed  CAS  Google Scholar 

  • Von Lubitz DK (1999) Adenosine and cerebral ischemia: therapeutic future or death of a brave concept? Eur J Pharmacol 365:9–25

    Google Scholar 

  • Von Lubitz DK, Beenhakker M, Lin RC, Carter MF, Paul IA, Bischofberger N, Jacobson KA (1996a) Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A1 receptor agonist. Eur J Pharmacol 302:43–48

    Google Scholar 

  • Von Lubitz DK, Lin RC, Paul IA, Beenhakker M, Boyd M, Bischofberger N, Jacobson KA (1996b) Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. Eur J Pharmacol 316:171–179

    Google Scholar 

  • Von Lubitz DK, Lin RC, Jacobson KA (1995) Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287:295–302

    Google Scholar 

  • Von Lubitz DK, Lin RC, Malman N, Ji XD, Carter MF, Jacobson KA (1994) Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia. Eur J Pharmacol 256:161–167

    Google Scholar 

  • Von Lubitz DK, Lin RC, Popik P, Carter MF, Jacobson KA (1994) Adenosine A3 receptor stimulation and cerebral ischemia. Eur J Pharmacol 263:59–67

    Google Scholar 

  • Von Lubitz DK, Marangos PJ (1990) Cerebral ischemia in gerbils: postischemic administration of cyclohexyl adenosine and 8-sulfophenyl-theophylline. J Mol Neurosci 2:53–59

    Google Scholar 

  • Wang J, Schaner ME, Thomassen S, Su S-F, Piquette-Miller M, Giacomini KM (1997) Functional and molecular characteristics of Na+-dependent nucleoside transporters. Pharmaceutical Research 14:1524–1532

    PubMed  CAS  Google Scholar 

  • Wiesner JB, Ugarkar BG, Castellino AJ, Barankiewicz J, Dumas DP, Gruber HE, Foster AC, Erion MD (1999) Adenosine kinase inhibitors as a novel approach to anticonvulsant therapy. J Pharmacol Exp Ther 289:1669–1677

    PubMed  CAS  Google Scholar 

  • Wiesner JB, Mullane KM, Foster AC (1997) A selective adenosine kinase inhibitor, GP3269, as a novel approach to anticonvulsant therapy. In: Okada Y (ed) The Role of Adenosine in the Nervous System, p 277, Elsevier, Amsterdam

    Google Scholar 

  • Wiesner JB, Zimring ST (1994) Inhibition of maximal electroshock seizures (MES) by A1 adenosine receptor agonists. Abs Soc Neurosci 20:668–669

    Google Scholar 

  • Wu LG, Saggau P (1994) Adenosine inhibits evoked synaptic transmission primarily by reducing presynaptic calcium influx in area CA1 of hippocampus. Neuron 12: 1139–1148

    PubMed  CAS  Google Scholar 

  • Yang SN, Dasgupta S, Lledo PM, Vincent JD, Fuxe K (1995) Reduction of dopamine D2 receptor transduction by activation of adenosine A2a receptors in stably A2a/D2 (long-form) receptor co-transfected mouse fibroblast cell lines: studies on intracellular calcium levels. Neuroscience 68:729–736

    PubMed  CAS  Google Scholar 

  • Zhang G, Franklin PH, Murray TF (1993) Manipulation of endogenous adenosine in the rat prepiriform cortex modulates seizure susceptibility. J Pharmacol Exp Ther 264:1415–1424

    PubMed  CAS  Google Scholar 

  • Zeng YC, Domenici MR, Frank C, Sagratella S, Scotti de Carolis A (1992) Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices. Life Sci 51:1073–1082

    PubMed  CAS  Google Scholar 

  • Zhou JG, Meno JR, Hsu SS, Winn HR (1994) Effects of theophylline and cyclohexyladenosine on brain injury following normo- and hyperglycemic ischemia: a histopathologic study in the rat. J Cereb Blood Flow Metab 14:166–173

    PubMed  CAS  Google Scholar 

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  1. A. C. Foster
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  2. L. P. Miller
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  3. J. B. Wiesner
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Editors and Affiliations

  1. Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI, 48105, USA

    Frank W. Marcoux (Vice President, Biology) (Vice President, Biology)

  2. Department of Neurology Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Dennis W. Choi

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Foster, A.C., Miller, L.P., Wiesner, J.B. (2002). Adenosine-Based Approaches to the Treatment of Neurodegenerative Disease. In: Marcoux, F.W., Choi, D.W. (eds) CNS Neuroprotection. Handbook of Experimental Pharmacology, vol 155. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-06274-6_7

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  • DOI: https://doi.org/10.1007/978-3-662-06274-6_7

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