{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:52:07Z","timestamp":1760187127798,"version":"3.41.2"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Sepracor, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>SEP\u2010227162 [<jats:italic>R<\/jats:italic>(\u2013)\u2010<jats:italic>O<\/jats:italic>\u2010desmethylvenlafaxine] is an enantiomer of the venlafaxine metabolite <jats:italic>O<\/jats:italic>\u2010desmethylvenlafaxine (ODV, Pristiq\u2122, Wyeth). This study compared the serotonin transporter (SERT) occupancy achieved by SEP\u2010227162 and ODV, at daily doses of 25, 50, 100, and 150 mg using [<jats:sup>11<\/jats:sup>C]DASB positron emission tomography (PET). Sixteen healthy male subjects participated in one of four dose groups (<jats:italic>N<\/jats:italic>\u2009=\u20094 per group) during which they were administered two doses of the study drug (SEP\u2010227162 or ODV). For each study drug, total daily doses of 25, 50, 100, and150 mg were studied. Subjects underwent three PET scans with [<jats:sup>11<\/jats:sup>C]DASB. A baseline, off\u2010medication, scan was performed prior to dosing and a [<jats:sup>11<\/jats:sup>C]DASB PET scan was performed after 72 hr at each dose level. [<jats:sup>11<\/jats:sup>C]DASB binding potential (BP<jats:sub>ND<\/jats:sub>) was calculated using the simplified reference tissue method. SERT occupancy was calculated as the change in BP<jats:sub>ND<\/jats:sub> (\u0394BP<jats:sub>ND<\/jats:sub>) from baseline scan to the on\u2010medication scan relative to the baseline BP<jats:sub>ND<\/jats:sub> value. SEP\u2010227162 and ODV significantly reduced regional distribution volumes and region BP<jats:sub>ND<\/jats:sub> values in a dose\u2010dependent manner. Across all doses ODV produced significantly greater SERT occupancy than SEP\u2010227162 (ANOVA <jats:italic>F<\/jats:italic>\u2009=\u200921.8, df\u2009=\u20091,23, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). The total daily dose required to provide 50% SERT occupancy was 24.8 mg for SEP\u2010227162 and 14.4 mg for ODV. In vitro data suggests a ratio of 3.3:1 for binding at human SERT for SEP\u2010227162 relative to ODV. Our study suggests a ratio of 1.7:1, highlighting the value of in vivo imaging in the drug development process.<\/jats:p>","DOI":"10.1002\/syn.22021","type":"journal-article","created":{"date-parts":[[2017,12,7]],"date-time":"2017-12-07T17:05:39Z","timestamp":1512666339000},"source":"Crossref","is-referenced-by-count":6,"title":["An open\u2010label positron emission tomography study to evaluate serotonin transporter occupancy following escalating dosing regimens of (<i>R<\/i>)\u2010(\u2013)\u2010<i>O<\/i>\u2010desmethylvenlafaxine and racemic <i>O<\/i>\u2010desmethylvenlafaxine"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-4197","authenticated-orcid":false,"given":"W. 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Lexington Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Maier","sequence":"additional","affiliation":[{"name":"MaierMetrics and Associates, LLC Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Paris","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanna","family":"Asmonga","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maureen","family":"May","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L.","family":"Himes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. Scott","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chester A.","family":"Mathis","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajesh","family":"Narendran","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Pittsburgh Pittsburgh Pennsylvania"},{"name":"Department of Radiology University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"228","article-title":"SPECT measurement of benzodiazepine receptors in human brain with [123\u2010I]iomazenil: Kinetic and equilibrium paradigms","volume":"35","author":"Abi\u2010Dargham A.","year":"1994","journal-title":"Journal of Nuclear Medicine"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199905)32:2<93::AID-SYN3>3.0.CO;2-C"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90511-8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0b013e32830cebed"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(88)90282-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.103382"},{"volume-title":"The human brain. 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