{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T16:23:30Z","timestamp":1787415810676,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015235","name":"Supernus Pharmaceuticals, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015235","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Efficacy of viloxazine ER (extended-release capsules; Qelbree\u00ae) for attention-deficit\/hyperactivity disorder (ADHD) is attributed to its ability to increase extracellular norepinephrine and dopamine in the medial prefrontal cortex by inhibiting norepinephrine transporters (NET); however, studies also suggest potentially relevant activity at serotonin (5-HT) receptors. In this study, we evaluated the target engagement by viloxazine at 5-HT2 receptor subtypes, in species with close similarities with humans, and whether viloxazine engages 5-HT2 receptor subtypes within a clinically relevant plasma concentration range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study utilized positron emission tomography (PET) and was conducted to measure the relationship between viloxazine plasma concentration and the changes in binding of the agonist radioligand [11C]CIMBI-36 to 5-HT2C\/5-HT2A receptors in the brain of Macaca fascicularis monkeys.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Viloxazine administration reduced the binding of [11C]CIMBI-36 at 5-HT2C receptors at a concentration 10- to 20-fold lower than at 5-HT2A receptors (EC50: 4.1 vs 45.1\u00a0\u03bcM, respectively), consistent with receptor binding affinities previously measured in vitro (Ki: 0.66 vs 16.0\u00a0\u03bcM, respectively). Unbound viloxazine plasma concentrations during these PET scans were compared to human unbound concentrations at doses used to treat ADHD. Our data suggest that at clinically relevant plasma concentrations, viloxazine occupies 60%-72% of 5-HT2C receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results demonstrate that at unbound viloxazine plasma concentrations comparable with those clinically relevant for the treatment of ADHD, viloxazine occupies a high proportion of 5-HT2C receptors. Occupancy of and potential functional activity at 5-HT2C receptors could therefore contribute to the therapeutic activity of viloxazine in addition to inhibition of NET.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ijnp\/pyag034","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:39:10Z","timestamp":1782214750000},"source":"Crossref","is-referenced-by-count":0,"title":["Viloxazine occupies the 5-HT2C receptor in the\n                    <i>Macaca fascicularis<\/i>\n                    brain in vivo: a [11C]CIMBI-36 positron emission tomography study"],"prefix":"10.1093","volume":"29","author":[{"given":"Jennie","family":"Garcia-Olivares","sequence":"first","affiliation":[{"name":"Supernus Pharmaceuticals, Inc. , Rockville, MD ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittney","family":"Yegla","sequence":"additional","affiliation":[{"name":"Supernus Pharmaceuticals, Inc. , Rockville, 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