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In vitro studies demonstrated that compound\n                    <jats:bold>5<\/jats:bold>\n                    exhibits high affinity for the 5\u2010HT\n                    <jats:sub>7<\/jats:sub>\n                    receptor (K\n                    <jats:sub>i<\/jats:sub>\n                    \u2009=\u200919\u2009nM), comparable to the reference ligand LP\u2010211, and potent inhibition of sodium channels, markedly stronger than that of phenytoin. Functional assays confirmed that compound\n                    <jats:bold>5<\/jats:bold>\n                    acts as a 5\u2010HT\n                    <jats:sub>7<\/jats:sub>\n                    receptor antagonist (K\n                    <jats:sub>b<\/jats:sub>\n                    \u2009=\u200987\u2009nM) with no detectable agonist activity. In addition, the compound showed negligible affinity for the serotonin transporter (SERT), indicating a favorable selectivity profile. Molecular docking studies revealed a stable binding mode of compound\n                    <jats:bold>5<\/jats:bold>\n                    within the orthosteric site of the 5\u2010HT\n                    <jats:sub>7<\/jats:sub>\n                    receptor, consistent with known GPCR interaction patterns. Modifications to compound\n                    <jats:bold>5<\/jats:bold>\n                    improved its safety by reducing hepatocytotoxicity in HepG2 cells. In vivo behavioral experiments demonstrated significant antidepressant\u2010like effects in the forced swim test and anxiolytic\u2010like effects in the four\u2010plate test in mice.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70366","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:41:08Z","timestamp":1792593668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Dual 5\u2010HT\n                    <sub>7<\/sub>\n                    Receptor Antagonist and Sodium Channel Inhibitor With Antidepressant\u2010 and Anxiolytic\u2010Like Activity and Reduced Hepatotoxicity"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1448-9826","authenticated-orcid":false,"given":"Anna","family":"Czopek","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy Jagiellonian University Medical College 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