{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:01:38Z","timestamp":1780376498356,"version":"3.54.1"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK41301"],"award-info":[{"award-number":["P30 DK41301"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["OT2OD24899"],"award-info":[{"award-number":["OT2OD24899"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004095","name":"Kyowa Hakko Kirin","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004095","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.ejphar.2021.174132","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T03:25:50Z","timestamp":1619753150000},"page":"174132","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Pharmacological characterization of naloxegol: In vitro and in vivo studies"],"prefix":"10.1016","volume":"903","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-1135","authenticated-orcid":false,"given":"Anna","family":"Costanzini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ruzza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim Azevedo","family":"Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sturaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-9550","authenticated-orcid":false,"given":"Davide","family":"Malfacini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-1993","authenticated-orcid":false,"given":"Catia","family":"Sternini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"De Giorgio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girolamo","family":"Cal\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.174132_bib1","doi-asserted-by":"crossref","DOI":"10.1111\/nmo.12443","article-title":"Site and mechanism of morphine tolerance in the gastrointestinal tract","author":"Akbarali","year":"2014","journal-title":"Neuro Gastroenterol. Motil."},{"key":"10.1016\/j.ejphar.2021.174132_bib2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0156897","article-title":"Characterisation of the novel mixed Mu-NOP peptide ligand dermorphin-N\/OFQ (DeNo)","volume":"11","author":"Bird","year":"2016","journal-title":"PloS One"},{"key":"10.1016\/j.ejphar.2021.174132_bib3","series-title":"Naldemedine: A Review in Opioid-Induced Constipation","author":"Blair","year":"2019"},{"key":"10.1016\/j.ejphar.2021.174132_bib4","series-title":"Methods in Molecular Biology","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/978-1-62703-086-1_18","article-title":"Chimeric G proteins in fluorimetric calcium assays: experience with opioid receptors","author":"Camarda","year":"2013"},{"key":"10.1016\/j.ejphar.2021.174132_bib5","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ejphar.2016.11.026","article-title":"Pharmacological studies on the NOP and opioid receptor agonist PWT2-[Dmt1]N\/OFQ(1-13)","volume":"794","author":"Cerlesi","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174132_bib6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2217\/pmt-2019-0045","article-title":"Subcutaneous methylnaltrexone for opioid-induced constipation in advanced-illness patients with or without active cancer","volume":"10","author":"Chamberlain","year":"2020","journal-title":"Pain Manag."},{"key":"10.1016\/j.ejphar.2021.174132_bib7","doi-asserted-by":"crossref","DOI":"10.1136\/gutjnl-2018-316824","article-title":"Assessing the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) in the treatment of opioid-induced constipation","author":"Chedid","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.ejphar.2021.174132_bib8","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/14656566.2020.1735354","article-title":"Evaluating naloxegol for the treatment of opioid-induced constipation","volume":"21","author":"Daniali","year":"2020","journal-title":"Expet Opin. Pharmacother."},{"key":"10.1016\/j.ejphar.2021.174132_bib9","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2020.564412","article-title":"Prevalence of therapeutic use of opioids in chronic non-cancer pain patients and associated factors: a systematic review and meta-analysis","author":"De Sola","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174132_bib10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/cpdd.204","article-title":"Safety, tolerability, and pharmacokinetics of multiple ascending doses of naloxegol","volume":"4","author":"Eldon","year":"2015","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"10.1016\/j.ejphar.2021.174132_bib11","doi-asserted-by":"crossref","DOI":"10.1177\/2050640618818305","article-title":"Pathophysiology and management of opioid-induced constipation: European expert consensus statement","author":"Farmer","year":"2019","journal-title":"United Eur. Gastroenterol. J."},{"key":"10.1016\/j.ejphar.2021.174132_bib12","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s11864-021-00816-5","article-title":"Insights into the use of peripherally acting \u03bc-opioid receptor antagonists (PAMORAs) in oncologic patients: from scientific evidence to real clinical practice","volume":"22","author":"Fern\u00e1ndez-Montes","year":"2021","journal-title":"Curr. Treat. Options Oncol."},{"key":"10.1016\/j.ejphar.2021.174132_bib13","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1124\/jpet.116.239061","article-title":"Pharmacologic profile of naloxegol, a peripherally acting \u03bc-opioid receptor antagonist, for the treatment of opioid-induced constipation","volume":"361","author":"Floettmann","year":"2017","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.174132_bib14","article-title":"Pharmacologic effects of naldemedine, a peripherally acting \u03bc-opioid receptor antagonist, in in vitro and in vivo models of opioid-induced constipation","volume":"31","author":"Kanemasa","year":"2019","journal-title":"Neuro Gastroenterol. Motil."},{"key":"10.1016\/j.ejphar.2021.174132_bib15","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1124\/jpet.119.264515","article-title":"Pharmacological profile of naldemedine, a peripherally acting \u03bc-opioid receptor antagonist: comparison with naloxone and naloxegol","volume":"373","author":"Kanemasa","year":"2020","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2021.174132_bib16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1000412","article-title":"Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research","volume":"8","author":"Kilkenny","year":"2010","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ejphar.2021.174132_bib17","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1053\/j.gastro.2016.02.031","article-title":"Bowel disorders","volume":"150","author":"Lacy","year":"2016","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ejphar.2021.174132_bib18","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1136\/gutjnl-2018-316001","article-title":"Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis","volume":"68","author":"Luthra","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.ejphar.2021.174132_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0132865","article-title":"Pharmacological profile of nociceptin\/orphanin FQ receptors interacting with G-proteins and \u03b2-arrestins 2","volume":"10","author":"Malfacini","year":"2015","journal-title":"PloS One"},{"key":"10.1016\/j.ejphar.2021.174132_bib20","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ejphar.2015.12.033","article-title":"Differences in the morphine-induced inhibition of small and large intestinal transit: involvement of central and peripheral \u03bc-opioid receptors in mice","volume":"771","author":"Matsumoto","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174132_bib21","doi-asserted-by":"crossref","first-page":"12522","DOI":"10.1074\/jbc.M109.059410","article-title":"Morphine-like opiates selectively antagonize receptor-arrestin interactions","volume":"285","author":"Molinari","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2021.174132_bib22","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1476-5381.2012.02115.x","article-title":"[Dmt 1 ]N\/OFQ(1-13)-NH 2\u00a0: a potent nociceptin\/orphanin FQ and opioid receptor universal agonist","volume":"168","author":"Molinari","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174132_bib23","doi-asserted-by":"crossref","DOI":"10.1124\/pr.55.4.4","article-title":"International union of pharmacology committee on receptor nomenclature and drug classification. XXXVIII. Update on terms and symbols in quantitative pharmacology","author":"Neubig","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.ejphar.2021.174132_bib24","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1021\/acs.bioconjchem.9b00519","article-title":"Tetrabranched hetero-conjugated peptides as bifunctional agonists of the NOP and mu opioid receptors","volume":"30","author":"Pacifico","year":"2019","journal-title":"Bioconjugate Chem."},{"key":"10.1016\/j.ejphar.2021.174132_bib25","doi-asserted-by":"crossref","DOI":"10.2147\/DDDT.S221278","article-title":"The use of peripheral \u03bc-opioid receptor antagonists (PAMORA) in the management of opioid-induced constipation: an update on their efficacy and safety","author":"Pergolizzi","year":"2020","journal-title":"Drug Des. Dev. Ther."},{"key":"10.1016\/j.ejphar.2021.174132_bib26","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.peptides.2017.11.020","article-title":"Cyclopeptide Dmt-[D-Lys-p-CF3-Phe-Phe-Asp]NH2, a novel G protein-biased agonist of the mu opioid receptor","volume":"101","author":"Piekielna-Ciesielska","year":"2018","journal-title":"Peptides"},{"key":"10.1016\/j.ejphar.2021.174132_bib27","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.247","article-title":"Pharmacological characterization of cebranopadol a novel analgesic acting as mixed nociceptin\/orphanin FQ and opioid receptor agonist","volume":"4","author":"Rizzi","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"10.1016\/j.ejphar.2021.174132_bib28","article-title":"Methylnaltrexone and naloxone for opioid-induced constipation in the critical care setting","volume":"12","author":"Saini","year":"2020","journal-title":"Cureus"},{"key":"10.1016\/j.ejphar.2021.174132_bib29","doi-asserted-by":"crossref","first-page":"360","DOI":"10.5414\/CP201646","article-title":"Low absolute bioavailability of oral naloxone in healthy subjects","volume":"50","author":"Smith","year":"2012","journal-title":"Int. J. Clin. Pharm. Ther."},{"key":"10.1016\/j.ejphar.2021.174132_bib30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/apt.15791","article-title":"Systematic review with meta-analysis: efficacy and safety of treatments for opioid-induced constipation","volume":"52","author":"Vijayvargiya","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"10.1016\/j.ejphar.2021.174132_bib31","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s11064-011-0627-7","article-title":"Study on the activation of the opioid receptors by a set of morphine derivatives in a well-defined assay system","volume":"37","author":"Zhang","year":"2012","journal-title":"Neurochem. Res."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921002855?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921002855?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:46:22Z","timestamp":1778636782000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921002855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":31,"alternative-id":["S0014299921002855"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174132","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pharmacological characterization of naloxegol: In vitro and in vivo studies","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174132","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"174132"}}