{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:11:15Z","timestamp":1773087075689,"version":"3.50.1"},"reference-count":38,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2007,11]]},"DOI":"10.1124\/jpet.107.121962","type":"journal-article","created":{"date-parts":[[2007,8,8]],"date-time":"2007-08-08T02:04:40Z","timestamp":1186538680000},"page":"708-719","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":70,"title":["Pharmacological Characterization of a Novel, Potent Adenosine A1 and A2A Receptor Dual Antagonist, 5-[5-Amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1 H)-one (ASP5854), in Models of Parkinson\u2019s Disease and Cognition"],"prefix":"10.1016","volume":"323","author":[{"given":"Takuma","family":"Mihara","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayoko","family":"Mihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Yarimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ritsuko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Akahane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinori","family":"Iwashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuya","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.107.121962_bib1","doi-asserted-by":"crossref","unstructured":"Chen C and Okayama H (1987) High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol 7: 2745\u20132752.","DOI":"10.1128\/MCB.7.8.2745"},{"key":"10.1124\/jpet.107.121962_bib2","doi-asserted-by":"crossref","unstructured":"Chen JF, Xu K, Petzer JP, Staal R, Xu YH, Beilstein M, Sonsalla PK, Castagnoli K, Castagnoli N, Jr., and Schwarzschild MA (2001) Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson\u2019s disease. J Neurosci 21: RC143.","DOI":"10.1523\/JNEUROSCI.21-10-j0001.2001"},{"key":"10.1124\/jpet.107.121962_bib3","doi-asserted-by":"crossref","unstructured":"Costenla AR, de Mendonca A, and Ribeiro JA (1999) Adenosine modulates synaptic plasticity in hippocampal slices from aged rats. Brain Res 851: 228\u2013234.","DOI":"10.1016\/S0006-8993(99)02194-0"},{"key":"10.1124\/jpet.107.121962_bib4","doi-asserted-by":"crossref","unstructured":"Ferre S, Fredholm BB, Morelli M, Popoli P, and Fuxe K (1997) Adenosine-dopamine receptor-receptor interactions as an integrative mechanism in the basal ganglia. Trends Neurosci 20: 482\u2013487.","DOI":"10.1016\/S0166-2236(97)01096-5"},{"key":"10.1124\/jpet.107.121962_bib5","doi-asserted-by":"crossref","unstructured":"Ferr\u00e9 S, von Euler G, Johansson B, Fredholm BB, and Fuxe K (1991) Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc Natl Acad Sci U S A 88: 7238\u20137241.","DOI":"10.1073\/pnas.88.16.7238"},{"key":"10.1124\/jpet.107.121962_bib6","doi-asserted-by":"crossref","unstructured":"Flagmeyer I, Haas HL, and Stevens DR (1997) Adenosine A1 receptor-mediated depression of corticostriatal and thalamostriatal glutamatergic synaptic potentials in vitro. Brain Res 778: 178\u2013185.","DOI":"10.1016\/S0006-8993(97)01060-3"},{"key":"10.1124\/jpet.107.121962_bib7","doi-asserted-by":"crossref","unstructured":"Fraser CM, Fisher A, Cooke MJ, Thompson ID, and Stone TW (1997) Purine modulation of dizocilpine effects on spontaneous alternation. Psychopharmacology 130: 334\u2013342.","DOI":"10.1007\/s002130050248"},{"key":"10.1124\/jpet.107.121962_bib8","doi-asserted-by":"crossref","unstructured":"Fredholm BB, Abbracchio MP, Burnstock G, Daly JW, Harden TK, Jacobson KA, Leff P, and Williams M (1994) Nomenclature and classification of purinoceptors. Pharmacol Rev 46: 143\u2013156.","DOI":"10.1016\/S0031-6997(25)06782-1"},{"key":"10.1124\/jpet.107.121962_bib9","doi-asserted-by":"crossref","unstructured":"Fredholm BB and Dunwiddie TV (1988) How does adenosine inhibit transmitter release? Trends Pharmacol Sci 9: 130\u2013134.","DOI":"10.1016\/0165-6147(88)90194-0"},{"key":"10.1124\/jpet.107.121962_bib10","doi-asserted-by":"crossref","unstructured":"Fredholm BB, Battig K, Holmen J, Nehlig A, and Zvartau EE (1999) Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev 51: 83\u2013133.","DOI":"10.1016\/S0031-6997(24)01396-6"},{"key":"10.1124\/jpet.107.121962_bib11","doi-asserted-by":"crossref","unstructured":"Hauser RA, Hubble JP, and Truong DD (2003) Randomized trial of the adenosine A(2A) receptor antagonist istradefylline in advanced PD. Neurology 61: 297\u2013303.","DOI":"10.1212\/01.WNL.0000081227.84197.0B"},{"key":"10.1124\/jpet.107.121962_bib12","doi-asserted-by":"crossref","unstructured":"Hayes ES (2003) Adenosine receptors and cardiovascular disease: the adenosine-1 receptor (A1) and A1 selective ligands. Cardiovasc Toxicol 3: 71\u201388.","DOI":"10.1385\/CT:3:1:71"},{"key":"10.1124\/jpet.107.121962_bib13","doi-asserted-by":"crossref","unstructured":"Hollins C and Stone TW (1980) Adenosine inhibition of gamma-aminobutyric acid release from slices of rat cerebral cortex. Br J Pharmacol 69: 107\u2013112.","DOI":"10.1111\/j.1476-5381.1980.tb10888.x"},{"key":"10.1124\/jpet.107.121962_bib14","doi-asserted-by":"crossref","unstructured":"Ikeda K, Kurokawa M, Aoyama S, and Kuwana Y (2002) Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson\u2019s disease. J Neurochem 80: 262\u2013270.","DOI":"10.1046\/j.0022-3042.2001.00694.x"},{"key":"10.1124\/jpet.107.121962_bib15","doi-asserted-by":"crossref","unstructured":"Iwashita A, Yamazaki S, Mihara K, Hattori K, Yamamoto H, Ishida J, Matsuoka N, and Mutoh S (2004) Neuroprotective effects of a novel poly(ADP-ribose) polymerase-1 inhibitor, 2-[3-[4-(4-chlorophenyl)-1-piperazinyl] propyl]-4(3 H)-quinazolinone (FR255595), in an in vitro model of cell death and in mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson\u2019s disease. J Pharmacol Exp Ther 309: 1067\u20131078.","DOI":"10.1124\/jpet.103.064642"},{"key":"10.1124\/jpet.107.121962_bib16","doi-asserted-by":"crossref","unstructured":"Kanda T, Tashiro T, Kuwana Y, and Jenner P (1998) Adenosine A2A receptors modify motor function in MPTP-treated common marmosets. Neuroreport 9: 2857\u20132860.","DOI":"10.1097\/00001756-199808240-00032"},{"key":"10.1124\/jpet.107.121962_bib17","doi-asserted-by":"crossref","unstructured":"Kase H (2001) New aspects of physiological and pathophysiological functions of adenosine A2A receptor in basal ganglia. Biosci Biotechnol Biochem 65: 1447\u20131457.","DOI":"10.1271\/bbb.65.1447"},{"key":"10.1124\/jpet.107.121962_bib18","doi-asserted-by":"crossref","unstructured":"Koga K, Kurokawa M, Ochi M, Nakamura J, and Kuwana Y (2000) Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats. Eur J Pharmacol 408: 249\u2013255.","DOI":"10.1016\/S0014-2999(00)00745-7"},{"key":"10.1124\/jpet.107.121962_bib19","doi-asserted-by":"crossref","unstructured":"Ledent C, Vaugeois JM, Schiffmann SN, Pedrazzini T, El Yacoubi M, Vanderhaeghen JJ, Costentin J, Heath JK, Vassart G, and Parmentier M (1997) Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor. Nature 388: 674\u2013678.","DOI":"10.1038\/41771"},{"key":"10.1124\/jpet.107.121962_bib20","doi-asserted-by":"crossref","unstructured":"Maemoto T, Tada M, Mihara T, Ueyama N, Matsuoka H, Harada K, Yamaji T, Shirakawa K, Kuroda S, Akahane A, et al. (2004) Pharmacological characterization of FR194921, a new potent, selective, and orally active antagonist for central adenosine A1 receptors. J Pharmacol Sci 96: 42\u201352.","DOI":"10.1254\/jphs.FP0040359"},{"key":"10.1124\/jpet.107.121962_bib21","doi-asserted-by":"crossref","unstructured":"Malenka RC, Kauer JA, Perkel DJ, and Nicoll RA (1989) The impact of postsynaptic calcium on synaptic transmission\u2013its role in long-term potentiation. Trends Neurosci 12: 444\u2013450.","DOI":"10.1016\/0166-2236(89)90094-5"},{"key":"10.1124\/jpet.107.121962_bib22","doi-asserted-by":"crossref","unstructured":"Mally J and Stone TW (1994) The effect of theophylline on parkinsonian symptoms. J Pharm Pharmacol 46: 515\u2013517.","DOI":"10.1111\/j.2042-7158.1994.tb03840.x"},{"key":"10.1124\/jpet.107.121962_bib23","doi-asserted-by":"crossref","unstructured":"Matsuoka N, Maeda N, Yamazaki M, Ohkubo Y, and Yamaguchi I (1992) Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks. J Pharmacol Exp Ther 263: 436\u2013444.","DOI":"10.1016\/S0022-3565(25)10368-6"},{"key":"10.1124\/jpet.107.121962_bib24","doi-asserted-by":"crossref","unstructured":"Morris RG, Anderson E, Lynch GS, and Baudry M (1986) Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature 319: 774\u2013776.","DOI":"10.1038\/319774a0"},{"key":"10.1124\/jpet.107.121962_bib25","doi-asserted-by":"crossref","unstructured":"Normile HJ and Barraco RA (1991) N6-Cyclopentyladenosine impairs passive avoidance retention by selective action at A1 receptors. Brain Res Bull 27: 101\u2013104.","DOI":"10.1016\/0361-9230(91)90288-U"},{"key":"10.1124\/jpet.107.121962_bib26","doi-asserted-by":"crossref","unstructured":"Onodera H and Kogure K (1988) Differential localization of adenosine A1 receptors in the rat hippocampus: quantitative autoradiographic study. Brain Res 458: 212\u2013217.","DOI":"10.1016\/0006-8993(88)90463-5"},{"key":"10.1124\/jpet.107.121962_bib27","doi-asserted-by":"crossref","unstructured":"Ovsepian SV, Anwyl R, and Rowan MJ (2004) Endogenous acetylcholine lowers the threshold for long-term potentiation induction in the CA1 area through muscarinic receptor activation: in vivo study. Eur J Neurosci 20: 1267\u20131275.","DOI":"10.1111\/j.1460-9568.2004.03582.x"},{"key":"10.1124\/jpet.107.121962_bib28","doi-asserted-by":"crossref","unstructured":"Phillis JW and Kostopoulos GK (1975) Adenosine as a putative transmitter in the cerebral cortex. Studies with potentiators and antagonists. Life Sci 17: 1085\u20131094.","DOI":"10.1016\/0024-3205(75)90329-X"},{"key":"10.1124\/jpet.107.121962_bib29","doi-asserted-by":"crossref","unstructured":"Popoli P, Gimenez-Llort L, Pezzola A, Reggio R, Martinez E, Fuxe K, and Ferr\u00e9S (1996) Adenosine A1 receptor blockade selectively potentiates the motor effects induced by dopamine D1 receptor stimulation in rodents. Neurosci Lett 218: 209\u2013213.","DOI":"10.1016\/S0304-3940(96)13143-8"},{"key":"10.1124\/jpet.107.121962_bib30","doi-asserted-by":"crossref","unstructured":"Rivkees SA, Price SL, and Zhou FC (1995) Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localization in the hippocampal formation, cerebral cortex, cerebellum, and basal ganglia. Brain Res 677: 193\u2013203.","DOI":"10.1016\/0006-8993(95)00062-U"},{"key":"10.1124\/jpet.107.121962_bib31","doi-asserted-by":"crossref","unstructured":"Schingnitz G, Kufner-Muhl U, Ensinger H, Lehr E, and Kuhn FJ (1991) Nucleoside. Nucleotide 10: 1067\u20131076.","DOI":"10.1080\/07328319108047244"},{"key":"10.1124\/jpet.107.121962_bib32","doi-asserted-by":"crossref","unstructured":"Seltzer B (2006) Cholinesterase inhibitors in the clinical management of Alzheimer\u2019s disease: importance of early and persistent treatment. J Int Med Res 34: 339\u2013347.","DOI":"10.1177\/147323000603400401"},{"key":"10.1124\/jpet.107.121962_bib33","doi-asserted-by":"crossref","unstructured":"Shimada JKN, Nonaka H, Shiozaki S, Yanagawa K, Kanda T, Kobayashi K, and Ichimura M (1997) Adenosine A2A antagonists with potent anti-cataleptic activity. Bioorg Med Chem Lett 7: 2349\u20132352.","DOI":"10.1016\/S0960-894X(97)00440-X"},{"key":"10.1124\/jpet.107.121962_bib34","doi-asserted-by":"crossref","unstructured":"Shiozaki S, Ichikawa S, Nakamura J, Kitamura S, Yamada K, and Kuwana Y (1999) Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology 147: 90\u201395.","DOI":"10.1007\/s002130051146"},{"key":"10.1124\/jpet.107.121962_bib35","doi-asserted-by":"crossref","unstructured":"Svenningsson P, Le Moine C, Fisone G, and Fredholm BB (1999) Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog Neurobiol 59: 355\u2013396.","DOI":"10.1016\/S0301-0082(99)00011-8"},{"key":"10.1124\/jpet.107.121962_bib36","doi-asserted-by":"crossref","unstructured":"Ukai M, Shinkai N, and Kameyama T (1998) Involvement of dopamine receptors in beneficial effects of tachykinins on scopolamine-induced impairment of alternation performance in mice. Eur J Pharmacol 350: 39\u201345.","DOI":"10.1016\/S0014-2999(98)00231-3"},{"key":"10.1124\/jpet.107.121962_bib37","doi-asserted-by":"crossref","unstructured":"Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl 367: 69\u201393.","DOI":"10.1111\/j.1365-201X.1971.tb11000.x"},{"key":"10.1124\/jpet.107.121962_bib38","doi-asserted-by":"crossref","unstructured":"Wang JH, Ma YY, and van den Buuse M (2006) Improved spatial recognition memory in mice lacking adenosine A2A receptors. Exp Neurol 199: 438\u2013445.","DOI":"10.1016\/j.expneurol.2006.01.005"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652434159X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652434159X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.107.121962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T22:27:01Z","timestamp":1740004021000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002235652434159X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["S002235652434159X"],"URL":"https:\/\/doi.org\/10.1124\/jpet.107.121962","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2007,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pharmacological Characterization of a Novel, Potent Adenosine A1 and A2A Receptor Dual Antagonist, 5-[5-Amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1 H)-one (ASP5854), in Models of Parkinson\u2019s Disease and Cognition","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.107.121962","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2007 The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}