{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:21:04Z","timestamp":1790763664099,"version":"4.1.0"},"reference-count":111,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Suven Life Sciences Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Serotonin (5-HT) plays an important role in the regulation of several basic functions of the central and peripheral nervous system. Among the 5-HT receptors, serotonin-6 (5-HT6) receptor has been an area of substantial research. 5-HT6 receptor is a G-protein-coupled receptor mediating its effects through diverse signaling pathways. Exceptional features of the receptors fueling drug discovery efforts include unique localization and specific distribution in the brain regions having a role in learning, memory, mood, and behavior, and the affinity of several clinically used psychotropic agents. Although non-clinical data suggest that both agonist and antagonist may have similar behavioral effects, most of the agents that entered clinical evaluation were antagonists. Schizophrenia was the initial target; more recently, cognitive deficits associated with Alzheimer\u2019s disease (AD) or other neurological disorders has been the target for clinically evaluated 5-HT6 receptor antagonists. Several 5-HT6 receptor antagonists (idalopirdine, intepirdine and latrepirdine) showed efficacy in alleviating cognitive deficits associated with AD in the proof-of-concept clinical studies; however, the outcomes of the subsequent phase 3 studies were largely disappointing. The observations from both non-clinical and clinical studies suggest that 5-HT6 receptor antagonists may have a role in the management of neuropsychiatric symptoms in dementia. Masupirdine, a selective 5-HT6 receptor antagonist, reduced agitation\/aggression-like behaviors in animal models, and a post hoc analysis of a phase 2 trial suggested potential beneficial effects on agitation\/aggression and psychosis in AD. This agent will be assessed in additional trials, and the outcome of the trials will inform the use of 5-HT6 receptor antagonists in the treatment of agitation in dementia of the Alzheimer\u2019s type.<\/jats:p>","DOI":"10.3390\/biom13020309","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T03:24:13Z","timestamp":1675740253000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders"],"prefix":"10.3390","volume":"13","author":[{"given":"Ramakrishna","family":"Nirogi","sequence":"first","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Jayarajan","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Shinde","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Rasheed","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-375X","authenticated-orcid":false,"given":"Venkata Ramalingayya","family":"Grandhi","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Benade","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod Kumar","family":"Goyal","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renny","family":"Abraham","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkat","family":"Jasti","sequence":"additional","affiliation":[{"name":"Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500034, Telangana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-4158","authenticated-orcid":false,"given":"Jeffrey","family":"Cummings","sequence":"additional","affiliation":[{"name":"Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, NV 89154, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","first-page":"357","article-title":"Ricerche sul secreto delle cellule enterocromaffini","volume":"51","author":"Erspamer","year":"1937","journal-title":"Boll. 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