{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:34:00Z","timestamp":1791488040416,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,9,17]],"date-time":"2013-09-17T00:00:00Z","timestamp":1379376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,10]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n An increasing body of evidence suggests that the purinergic receptor\n P2X<\/jats:styled-content>\n , ligand\u2010gated ion channel, 7 (\n P2X7<\/jats:styled-content>\n ) in the\n CNS<\/jats:styled-content>\n may play a key role in neuropsychiatry, neurodegeneration and chronic pain. In this study, we characterized\n JNJ<\/jats:styled-content>\n \u201047965567, a centrally permeable, high\u2010affinity, selective\n P2X7<\/jats:styled-content>\n antagonist.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n We have used a combination of\n in vitro<\/jats:italic>\n assays (calcium flux, radioligand binding, electrophysiology,\n IL<\/jats:styled-content>\n \u20101\u03b2 release) in both recombinant and native systems. Target engagement of\n JNJ<\/jats:styled-content>\n \u201047965567 was demonstrated by\n ex vivo<\/jats:italic>\n receptor binding autoradiography and\n in vivo<\/jats:italic>\n blockade of\n Bz<\/jats:styled-content>\n \u2010\n ATP<\/jats:styled-content>\n induced\n IL<\/jats:styled-content>\n \u20101\u03b2 release in the rat brain. Finally, the efficacy of\n JNJ<\/jats:styled-content>\n \u201047965567 was tested in standard models of depression, mania and neuropathic pain.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n JNJ<\/jats:styled-content>\n \u201047965567 is potent high affinity (\n \n pK\n i<\/jats:sub>\n <\/jats:styled-content>\n 7.9 \u00b1 0.07), selective human\n P2X7<\/jats:styled-content>\n antagonist, with no significant observed speciation. In native systems, the potency of the compound to attenuate\n IL<\/jats:styled-content>\n \u20101\u03b2 release was 6.7 \u00b1 0.07 (human blood), 7.5 \u00b1 0.07 (human monocytes) and 7.1 \u00b1 0.1 (rat microglia).\n JNJ<\/jats:styled-content>\n \u201047965567 exhibited target engagement in rat brain, with a brain\n \n EC\n 50<\/jats:sub>\n <\/jats:styled-content>\n of 78 \u00b1 19\u2009ng\u00b7mL\n \u22121<\/jats:sup>\n (\n P2X7<\/jats:styled-content>\n receptor autoradiography) and functional block of\n Bz<\/jats:styled-content>\n \u2010\n ATP<\/jats:styled-content>\n induced\n IL<\/jats:styled-content>\n \u20101\u03b2 release.\n JNJ<\/jats:styled-content>\n \u201047965567 (30\u2009mg\u00b7kg\n \u22121<\/jats:sup>\n ) attenuated amphetamine\u2010induced hyperactivity and exhibited modest, yet significant efficacy in the rat model of neuropathic pain. No efficacy was observed in forced swim test.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Implications<\/jats:title>\n \n JNJ<\/jats:styled-content>\n \u201047965567 is centrally permeable, high affinity\n P2X7<\/jats:styled-content>\n antagonist that can be used to probe the role of central\n P2X7<\/jats:styled-content>\n in rodent models of\n CNS<\/jats:styled-content>\n pathophysiology.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12314","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T10:31:27Z","timestamp":1376476287000},"page":"624-640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":194,"title":["Pharmacological characterization of a novel centrally permeable\n P2X7<\/scp>\n receptor antagonist:\n JNJ<\/scp>\n \u201047965567"],"prefix":"10.1111","volume":"170","author":[{"given":"Anindya","family":"Bhattacharya","sequence":"first","affiliation":[{"name":"Neuroscience 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