{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:29:41Z","timestamp":1791599381382,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Radiprodil is a GluN2B subunit selective NMDA receptor negative allosteric modulator which is currently under clinical investigation as a possible anti\u2010epileptic drug for paediatric use. Our goal was to investigate the inhibition of dopaminergic neuron NMDA responses by radiprodil.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Whole\u2010cell and outside\u2010out patch\u2010clamp recordings from substantia nigra dopaminergic neurons in acute mid\u2010brain slices from neonatal male rats were used to investigate radiprodil action. Radiprodil action was analysed using a \u2018hypercube\u2019 model with explicit receptor GluN2B subunit\u2010dependent binding steps for agonist and antagonist and allosteric constant describing the effect of radiprodil on agonist binding and receptor channel gating and a 2nd binding site for radiprodil that may mediate partial reversal of the radiprodil inhibitory effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Radiprodil produced a concentration\u2010dependent partial inhibition with about 40% maximum at concentrations between 30 and 100\u2009nM. Surprisingly, at higher radiprodil concentrations, the inhibition decreased. Radiprodil (30\u2009nM) also caused a 12% decrease in single channel current.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>The results are described by a two\u2010binding site model assuming radiprodil inhibits receptor activation by binding to the GluN2B subunit whilst reducing inhibition by binding to a secondary site, which may or may not be on the receptor. We conclude that NMDA receptor allosteric modulators such as radiprodil can display a combination of inhibitory and reversal of inhibitory effects, depending on drug concentration and receptor subunit combinations. These properties may give some allosteric drugs a unique profile of action, which could be advantageous in some clinical circumstances.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70630","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:02:07Z","timestamp":1786687327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NMDA receptor subunit\u2010dependent analysis of radiprodil inhibition in neonatal male rat substantia nigra dopaminergic neurons"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6459-128X","authenticated-orcid":false,"given":"Bangyuan","family":"Liu","sequence":"first","affiliation":[{"name":"Research Department of Neuroscience, Physiology and Pharmacology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-1615","authenticated-orcid":false,"given":"Alasdair J.","family":"Gibb","sequence":"additional","affiliation":[{"name":"Research Department of Neuroscience, Physiology and Pharmacology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50998"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf355"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1000"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16361"},{"key":"e_1_2_11_6_1","unstructured":"Bradford A. M.(2006).Molecular pharmacology of a novel NR2B\u2010selective NMDA receptor antagonist [Durham University]."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.144618"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01640"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.109027"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1993.tb00479.x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702164"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.103.038679"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_11_14_1","unstructured":"Farkas S. H. Nagy J. Kolok S. Fodor L. Gere A. Fazekas K. Kiss B. Galgoczy K. Hajos N. Karsai E. G. Saghy K. Szalai G. B. Domany G. Felmerai L. &Szombathelyi Z.(2003).RGH\u2010896 is a novel potent and selective NR2B\u2010NMDA antagonist with efficacy in neuropathic pain models. Program No. 382.8. 2003 Neuroscience Meeting Planner."},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1163\/156856005774649304"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00031"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP276093"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(88)90307-7"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.17-01-00204.1997"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.04-11-02877.1984"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614042113"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00762-9"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.121.001000"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.035"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000131"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201812032"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01614-3"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaf1067"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3009-07.2007"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.240487"},{"key":"e_1_2_11_31_1","unstructured":"Horvath C.(2004).PAIN Practice 3rd World Congress Barcelona Spain."},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.267864"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1329209"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.095554"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10180"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/npr2.12232"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.03.013"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.117069"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182887"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00304.x"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2707"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/3661"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.05.017"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.08.003"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00210"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x20943823"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.22-14-05955.2002"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0449-5"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.120.000218"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34711"},{"key":"e_1_2_11_52_1","volume-title":"Trafficking and targeting of NMDA receptors","author":"Petralia R. S.","year":"2009"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.07.021"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17679"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.124.001019"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.234062"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.2.555"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2021.03.001"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.250522"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278168"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107971"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.113"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70630","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.70630","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.70630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:02:09Z","timestamp":1786687329000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.70630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":61,"alternative-id":["10.1111\/bph.70630"],"URL":"https:\/\/doi.org\/10.1111\/bph.70630","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"assertion":[{"value":"2025-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bph.70630"}}