{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:44:13Z","timestamp":1777394653321,"version":"3.51.4"},"reference-count":69,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2017,6,23]]},"abstract":"<jats:p>\n                    Discovery of 5-HT\n                    <jats:sub>6<\/jats:sub>\n                    receptor subtype and its exclusive localization within the central nervous system led to extensive investigations of its role in Alzheimer\u2019s disease, schizophrenia, and obesity. In the present study, we present preclinical evaluation of a novel highly-potent and highly-selective 5-HT\n                    <jats:sub>6<\/jats:sub>\n                    R antagonist, AVN-492. The affinity of AVN-492 to bind to 5-HT\n                    <jats:sub>6<\/jats:sub>\n                    R (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    \u200a=\u200a91 pM) was more than three orders of magnitude higher than that to bind to the only other target, 5-HT\n                    <jats:sub>2B<\/jats:sub>\n                    R, (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    \u200a=\u200a170 nM). Thus, the compound displayed great 5-HT\n                    <jats:sub>6<\/jats:sub>\n                    R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc. AVN-492 demonstrates good\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    ADME profile with high oral bioavailability and good brain permeability in rodents. In behavioral tests, AVN-492 shows anxiolytic effect in elevated plus-maze model, prevents an apomorphine-induced disruption of startle pre-pulse inhibition (the PPI model) and reverses a scopolamine- and MK-801-induced memory deficit in passive avoidance model. No anti-obesity effect of AVN-492 was found in a murine model. The data presented here strongly indicate that due to its high oral bioavailability, extremely high selectivity, and potency to block the 5-HT\n                    <jats:sub>6<\/jats:sub>\n                    receptor, AVN-492 is a very promising tool for evaluating the role the 5-HT6 receptor might play in cognitive and neurodegenerative impairments. AVN-492 is an excellent drug candidate to be tested for treatment of such diseases, and is currently being tested in Phase I trials.\n                  <\/jats:p>","DOI":"10.3233\/jad-161262","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T14:46:23Z","timestamp":1495809983000},"page":"1043-1063","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["AVN-492, A Novel Highly Selective 5-HT\n                    <sub>6<\/sub>\n                    R Antagonist: Preclinical Evaluation"],"prefix":"10.1177","volume":"58","author":[{"given":"Alexandre V.","family":"Ivachtchenko","sequence":"first","affiliation":[{"name":"Alla Chem LLC, Hallandale Beach, FL, USA"},{"name":"Avineuro Pharmaceuticals, Inc., HallandaleBeach, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Okun","sequence":"additional","affiliation":[{"name":"ChemDiv Inc 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