{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:50:06Z","timestamp":1791561006737,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Positive allosteric modulators bind to secondary binding sites on the receptor and alter receptor conformation and activation, changing agonist potency and efficacy. PTC\u2010174 is a novel NMDA receptor positive allosteric modulator that particularly enhances activity of receptors containing GluN2C or GluN2D subunits. We have investigated potentiation by PTC\u2010174 of dopaminergic neuron NMDA responses, where receptors are likely to be GluN1\/GluN2B\/GluN2D triheteromeric receptors.<\/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 6\u2010 to 8\u2010day\u2010old rats were used to investigate the effects of PTC\u2010174 on NMDA responses and on NMDA receptor\u2010mediated excitatory post\u2010synaptic currents (EPSCs). A new \u2018hypercube\u2019 model with explicit receptor subunit\u2010dependent binding steps for agonists and allosteric modulators was used to describe the effects of PTC\u2010174.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>As expected, PTC\u2010174 potentiated NMDA responses, with a &gt;1.7\u2010fold increase at 200\u2010\u03bcM NMDA. The effect was independent of inhibition by the GluN2B\u2010selective NAM ifenprodil when the two drugs were co\u2010applied. In outside\u2010out patches, PTC\u2010174 increased channel open probability without altering the unitary current amplitude. PTC\u2010174 prolonged the decay of NMDA receptor\u2010mediated EPSCs and increased EPSC charge transfer. The results were described by a two\u2010binding site subunit\u2010specific \u2018hypercube\u2019 model that suggests PTC\u2010174 reduces agonist microscopic affinity but enhances channel\u2010gating efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>The main implication of the results in this paper is that PAMs like PTC\u2010174 have the potential to enhance NMDA receptor signalling at substantia nigra dopaminergic neurons in vivo and so could enhance basal ganglia dopamine signalling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70615","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:28:58Z","timestamp":1785896938000},"page":"6481-6500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Potentiation effects of the positive allosteric modulator PTC\u2010174 on NMDA receptors in neonatal male rat substantia nigra dopaminergic neurons"],"prefix":"10.1111","volume":"183","author":[{"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":[[2026,8,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70231"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(25)13660-2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.144618"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107994"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1993.tb00479.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1359647"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.103.038679"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.17441"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-895X(25)09575-6"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81052-1"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2004.11.004"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.5234-06.2007"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108861"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1173-17.2017"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(88)90307-7"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.17-01-00204.1997"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.04-11-02877.1984"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201812032"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01614-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3035-08.2008"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp017980"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.267864"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2017.06.035"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1329209"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.095554"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.19-04-01165.1999"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.13-02-00674.1993"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/346565a0"},{"key":"e_1_2_11_30_1","doi-asserted-by":"crossref","unstructured":"Lilley E. 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