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The structure of the complex was determined by X\u2010ray crystallography. The selectivity of LT\u2010102 was evaluated by hERG tail current recording and kinase\u2010inhibition assays. The electrophysiological characterization of LT\u2010102 was characterized by patch\u2010clamp recording in mouse hippocampal slices. The expression and phosphorylation levels of proteins were examined by Western blotting. Cognitive function was assessed using the Morris water maze and novel object recognition tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LT\u2010102 is a novel and selective AMPAR potentiator with little agonistic effect, which binds to the allosteric site formed by the intradimer interface of AMPAR's GluA2 subunit. Treatment with LT\u2010102 facilitated long\u2010term potentiation in mouse hippocampal slices and reversed cognitive deficits in a phencyclidine\u2010induced mouse model. Additionally, LT\u2010102 treatment increased the protein level of brain\u2010derived neurotrophic factor and the phosphorylation of GluA1 in primary neurons and hippocampal tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We conclude that LT\u2010102 ameliorates cognitive impairments in a phencyclidine\u2010induced model of schizophrenia by enhancing synaptic function, which could make it a potential therapeutic candidate for CIAS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14713","type":"journal-article","created":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T21:01:00Z","timestamp":1713128460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazole\u2010propionic acid receptor (<scp>AMPAR<\/scp>) potentiator <scp>LT<\/scp>\u2010102: A promising therapeutic agent for treating cognitive impairment associated with schizophrenia"],"prefix":"10.1111","volume":"30","author":[{"given":"Xueyu","family":"Qi","sequence":"first","affiliation":[{"name":"Affiliated Mental Health Center &amp; Hangzhou Seventh People's Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain\u2010Machine Integration, State Key Laboratory of Brain\u2010Machine Intelligence Zhejiang University  Hangzhou China"},{"name":"NHC and CAMS Key Laboratory of Medical Neurobiology Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Yu","sequence":"additional","affiliation":[{"name":"Affiliated Mental Health Center &amp; Hangzhou Seventh People's Hospital and School of Brain Science and Brain Medicine Zhejiang University School of Medicine  Hangzhou China"},{"name":"Liangzhu Laboratory, MOE Frontier 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