{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:30Z","timestamp":1772160690353,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2024,9]]},"abstract":"Abstract<\/jats:title>\n \n Here, we describe the characterization of a radioligand selective for GluN2B\u2010containing NMDA receptors, 3\u2010[\n 3<\/jats:sup>\n H] 1\u2010(azetidin\u20101\u2010yl)\u20102\u2010(6\u2010(4\u2010fluoro\u20103\u2010methyl\u2010phenyl)pyrrolo[3,2\u2010\n b<\/jats:italic>\n ]pyridin\u20101\u2010yl)ethanone ([\n 3<\/jats:sup>\n H]\u2010JNJ\u2010 GluN2B\u20105). In rat cortical membranes, the compound bound to a single site, and the following kinetic parameters were measured; association rate constant\n K<\/jats:italic>\n on<\/jats:sub>\n \u2009=\u20090.0066\u2009\u00b1\u20090.0006\u2009min\n \u22121<\/jats:sup>\n \u2009nM\n \u22121<\/jats:sup>\n , dissociation rate constant\n K<\/jats:italic>\n off<\/jats:sub>\n \u2009=\u20090.0210\u2009\u00b1\u20090.0001\u2009min\n \u22121<\/jats:sup>\n indicating calculated\n K<\/jats:italic>\n D<\/jats:sub>\n \u2009=\u2009\n K<\/jats:italic>\n off<\/jats:sub>\n \/\n K<\/jats:italic>\n on<\/jats:sub>\n \u2009=\u20093.3\u2009\u00b1\u20090.4\u2009nM, (mean\u2009\u00b1\u2009SEM,\n n<\/jats:italic>\n \u2009=\u20093). The equilibrium dissociation constant determined from saturation binding experiments in rat cortex was\n K<\/jats:italic>\n D<\/jats:sub>\n of 2.6\u2009\u00b1\u20090.3\u2009nM (mean\u2009\u00b1\u2009SEM,\n n<\/jats:italic>\n \u2009=\u20093). In contrast to the widely used GluN2B radioligand [\n 3<\/jats:sup>\n H]\u2010Ro 25\u20106981, whose affinity\n K<\/jats:italic>\n i<\/jats:sub>\n for sigma 1 and sigma 2 receptors are 2 and 189\u2009nM, respectively, [\n 3<\/jats:sup>\n H]\u2010JNJ\u2010GluN2B\u20105 exhibits no measurable affinity for sigma 1 and sigma 2 receptors (\n K<\/jats:italic>\n i<\/jats:sub>\n \u2009>\u200910\u2009\u03bcM for both) providing distinct selectivity advantages. Anatomical distribution of [\n 3<\/jats:sup>\n H]\u2010JNJ\u2010GluN2B\u20105 binding sites in rat, mouse, dog, monkey, and human brain tissue was studied using in\u00a0vitro autoradiography, which showed high specific binding in the hippocampus and cortex and negligible binding in the cerebellum. Enhanced selectivity for GluN2B\u2010containing receptors translated to a good signal\u2010to\u2010noise ratio in both in\u00a0vitro radioligand binding and in\u00a0vitro autoradiography assays. In conclusion, [\n 3<\/jats:sup>\n H]\u2010JNJ\u2010GluN2B\u20105 is a high\u2010affinity GluN2B radioligand with excellent signal\u2010to\u2010noise ratio and unprecedented selectivity.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>","DOI":"10.1111\/jnc.16129","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T04:40:08Z","timestamp":1716266408000},"page":"2654-2670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of tritiated JNJ\u2010GluN2B\u20105 (3\u2010[\n 3<\/sup>\n H] 1\u2010(azetidin\u20101\u2010yl)\u20102\u2010(6\u2010(4\u2010fluoro\u20103\u2010methyl\u2010phenyl)pyrrolo[3,2\u2010\n b<\/i>\n ]pyridin\u20101\u2010yl)ethanone), a high affinity GluN2B radioligand with selectivity over sigma receptors"],"prefix":"10.1111","volume":"168","author":[{"given":"Jeffrey","family":"Schoellerman","sequence":"first","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Lord","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anindya","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brice","family":"Stenne","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L.","family":"Wall","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Rech","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Letavic","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Bonaventure","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8913-0738","authenticated-orcid":false,"given":"Bartosz","family":"Balana","sequence":"additional","affiliation":[{"name":"Neuroscience Discovery Janssen Research & Development, LLC La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2020.1811234"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0014\u20102999(97)00045\u20109"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0000000000001496"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.119.235143"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00114a018"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.8b00542"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b02113"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959\u20104388(00)00215\u20104"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(91)90127-F"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(82)91017\u20104"},{"key":"e_1_2_11_12_1","volume-title":"Multiple comparisons using R","author":"Frank Bretz T. 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