{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:15:59Z","timestamp":1791357359466,"version":"4.3.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T00:00:00Z","timestamp":1454630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>SEP\u2010432 is a triple monoamine reuptake inhibitor of norepinephrine (NE), serotonin (5\u2010HT), and dopamine (DA), based on <jats:italic>in\u00a0vitro<\/jats:italic> binding studies. We sought evidence that SEP\u2010432 engages these monoamine systems by measuring concentrations of monoamines and\/or their main metabolites in cerebrospinal fluid (CSF) and plasma and comparing results to duloxetine, a dual reuptake inhibitor of NE and 5\u2010HT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen healthy normal subjects received either SEP\u2010432 (300\u00a0mg\/day), duloxetine (60\u00a0mg\/day), or placebo for 14\u00a0days in\u2010clinic (double blind) with CSF and plasma collections at baseline (single lumbar puncture) and Day 14 (24\u2010h CSF and plasma collection). Concentrations of monoamines and their metabolites, as well as pharmacokinetic concentrations of SEP\u2010432 and metabolite, were quantified by liquid chromatography\u2013tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to placebo in the Day 14 area under the curve 24\u2010h (AUC<jats:sub>0\u201324\u00a0h<\/jats:sub>) analysis, SEP\u2010432 significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) decreased the NE metabolite dihydroxyphenylglycol (DHPG) in CSF and plasma, decreased 5\u2010HT in plasma, and did not affect DA metabolites, while duloxetine had significant effects on DHPG and 5\u2010HT. Time\u2010matched baseline to Day 14 biomarker comparisons confirmed these findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CSF monoamine biomarkers confirmed central NET activity for SEP\u2010432 and duloxetine's dual reuptake inhibition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12513","type":"journal-article","created":{"date-parts":[[2016,2,5]],"date-time":"2016-02-05T13:29:39Z","timestamp":1454678979000},"page":"404-412","source":"Crossref","is-referenced-by-count":6,"title":["Exploratory Biomarker Study of the Triple Reuptake Inhibitor SEP\u2010432 Compared to the Dual Reuptake Inhibitor Duloxetine in\u00a0Healthy Normal Subjects"],"prefix":"10.1111","volume":"22","author":[{"given":"John J.","family":"Sramek","sequence":"first","affiliation":[{"name":"Worldwide Clinical Trials Beverly Hills CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry W.","family":"Hardy","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Marlborough MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bieck","sequence":"additional","affiliation":[{"name":"Worldwide Clinical Trials Beverly Hills CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Zamora","sequence":"additional","affiliation":[{"name":"Worldwide Clinical Trials Drug Development Solutions San Antonio and Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Versavel","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Marlborough MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahnavi","family":"Kharidia","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Marlborough MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Grinnell","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Marlborough MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Luan","family":"Chen","sequence":"additional","affiliation":[{"name":"Sunovion Pharmaceuticals Marlborough MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Worldwide Clinical Trials Drug Development Solutions San Antonio and Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ding","sequence":"additional","affiliation":[{"name":"Worldwide Clinical Trials Beverly Hills CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal R.","family":"Cutler","sequence":"additional","affiliation":[{"name":"Worldwide Clinical Trials Beverly Hills CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,5]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"101","article-title":"The Harold E. 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