{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:14:16Z","timestamp":1792174456839,"version":"4.4.0"},"reference-count":80,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Eating Disorders"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Test the efficacy of the selective orexin 1 receptor (OX1R) antagonist (SO1RA) nivasorexant in an animal model of binge\u2010eating disorder (BED) and study its dose\u2013response relationship considering free brain concentrations and calculated OX1R occupancy. Compare nivasorexant's profile to that of other, structurally diverse SO1RAs. Gain understanding of potential changes in orexin\u2010A (OXA) neuropeptide and deltaFosB (\u0394FosB) protein expression possibly underlying the development of the binge\u2010eating phenotype in the rat model used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Binge\u2010like eating of highly palatable food (HPF) in rats was induced through priming by intermittent, repeated periods of dieting and access to HPF, followed by an additional challenge with acute stress. Effects of nivasorexant were compared to the SO1RAs ACT\u2010335827 and IDOR\u20101104\u20102408. OXA expression in neurons and neuronal fibers as well as \u0394FosB and OXA\u2010\u0394FosB co\u2010expression was studied in relevant brain regions using immuno\u2010 or immunofluorescent histochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All SO1RAs dose\u2010dependently reduced binge\u2010like eating with effect sizes comparable to the positive control topiramate, at unbound drug concentrations selectively blocking brain OX1Rs. Nivasorexant's efficacy was maintained upon chronic dosing and under conditions involving more frequent stress exposure. Priming for binge\u2010like eating or nivasorexant treatment resulted in only minor changes in OXA or \u0394FosB expression in few brain areas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Selective OX1R blockade reduced binge\u2010like eating in rats. Neither \u0394FosB nor OXA expression proved to be a useful classifier for their binge\u2010eating phenotype. The current results formed the basis for a clinical phase II trial in BED, in which nivasorexant was unfortunately not efficacious compared with placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Public Significance<\/jats:title>\n                    <jats:p>Nivasorexant is a new investigational drug for the treatment of binge\u2010eating disorder (BED). It underwent clinical testing in a phase II proof of concept trial in humans but was not efficacious compared with placebo. The current manuscript investigated the drug's efficacy in reducing binge\u2010like eating behavior of a highly palatable sweet and fat diet in a rat model of BED, which initially laid the foundation for the clinical trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/eat.24181","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T07:59:17Z","timestamp":1709884757000},"page":"1418-1432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evaluating the efficacy of the selective orexin 1 receptor antagonist nivasorexant in an animal model of binge\u2010eating disorder"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9923-6555","authenticated-orcid":false,"given":"Michel Alexander","family":"Steiner","sequence":"first","affiliation":[{"name":"CNS Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5414-2368","authenticated-orcid":false,"given":"Luca","family":"Botticelli","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, School of Pharmacy University of Camerino  Camerino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Bergamini","sequence":"additional","affiliation":[{"name":"CNS Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8484-7513","authenticated-orcid":false,"given":"Emanuela","family":"Micioni Di Bonaventura","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, School of Pharmacy University of Camerino  Camerino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gatfield","sequence":"additional","affiliation":[{"name":"CNS Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi T.","family":"Williams","sequence":"additional","affiliation":[{"name":"CNS Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Treiber","sequence":"additional","affiliation":[{"name":"CNS Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Vaillant","sequence":"additional","affiliation":[{"name":"CNS Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6180-828X","authenticated-orcid":false,"given":"Carlo","family":"Cifani","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, School of Pharmacy University of Camerino  Camerino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8044-1206","authenticated-orcid":false,"given":"Maria Vittoria","family":"Micioni Di Bonaventura","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, School of Pharmacy University of Camerino  Camerino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06310"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03749.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.06.049"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genhosppsych.2008.02.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00446.2012"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2461"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6096-08.2009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19m12813"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2020.04.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200110000-00006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00456"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1442-y"},{"key":"e_1_2_10_15_1","unstructured":"ClinicalTrials.gov. 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