{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T14:07:56Z","timestamp":1775311676206,"version":"3.50.1"},"reference-count":82,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T00:00:00Z","timestamp":1544745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["502-03\/1-156-04\/502-14-297"],"award-info":[{"award-number":["502-03\/1-156-04\/502-14-297"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005888","name":"Uniwersytet Medyczny w Lodzi","doi-asserted-by":"publisher","award":["503\/1-156-04\/503-11-001"],"award-info":[{"award-number":["503\/1-156-04\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The endogenous opioid system (EOS) is considered being a crucial element involved in the pathophysiology of irritable bowel syndrome (IBS) as it regulates gastrointestinal (GI) homeostasis through modulation of motility and water and ion secretion\/absorption. Along with opioid receptors (ORs), the following components of EOS can be distinguished: 1. endogenous opioid peptides (EOPs), namely enkephalins, endorphins, endomorphins and dynorphins, and 2. peptidases, which regulate the metabolism (synthesis and degradation) of EOPs. Enkephalins, which are \u03b4\u2010opioid receptors agonists, induce significant effects in the GI tract as they act as potent pro\u2010absorptive neurotransmitters. The action of enkephalins and other EOPs is limited, since EOPs are easily and rapidly inactivated by a natural metalloendopeptidase (enkephalinase\/neprilysin) and aminopeptidase N. Studies show that the activity of EOPs can be enhanced by inhibition of these enzymes. In this review, we discuss the antidiarrheal and antinociceptive potential of enkephalinase inhibitors. Furthermore, our review is to answer the question whether enkephalinase inhibitors may be helpful in the future treatment of diarrhea predominant functional GI disorders.<\/jats:p>","DOI":"10.1111\/nmo.13526","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T03:15:03Z","timestamp":1544757303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Enkephalinase inhibitors, potential therapeutics for the future treatment of diarrhea predominant functional gastrointestinal disorders"],"prefix":"10.1111","volume":"31","author":[{"given":"Agata","family":"Szymaszkiewicz","sequence":"first","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Storr","sequence":"additional","affiliation":[{"name":"Department of Medicine Ludwig Maximilians University Munich Munich Germany"},{"name":"Center of Endoscopy Starnberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8443-4417","authenticated-orcid":false,"given":"Jakub","family":"Fichna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5939-791X","authenticated-orcid":false,"given":"Marta","family":"Zielinska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529709011203"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.061"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(15)31649-8"},{"issue":"6","key":"e_1_2_13_5_1","first-page":"RA125\u201031","article-title":"The brain\u2010gut axis in irritable bowel syndrome\u2013clinical aspects","volume":"10","author":"Mach T","year":"2004","journal-title":"Med Sci Monit"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/SGA.0000000000000017"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12529-011-9195-0"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881110367726"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-013-0753-x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-012-1172-4"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2012.01.013"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.09.007"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.05.042"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00227-3"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90509-Z"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5935"},{"key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2174\/1389557516666160804165318","article-title":"The role of MOP and DOP receptors in treatment of diarrhea\u2010predominant irritable bowel syndrome","volume":"16","author":"Jarmu\u017c A","journal-title":"Mini Rev Med Chem"},{"issue":"1","key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0031-6997(25)00449-1","article-title":"Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical pharmacology","volume":"45","author":"Roques BP","year":"1993","journal-title":"Pharmacol Rev"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/288286a0"},{"issue":"3","key":"e_1_2_13_20_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0022-3565(25)22997-4","article-title":"Effects of [N\u2010(L\u2010(1\u2010carboxy\u20102\u2010phenyl)ethyl]\u2010L\u2010phenylalanyl\u2010beta\u2010alanine (SCH32615), a neutral endopeptidase (enkephalinase) inhibitor, on levels of enkephalin, encrypted enkephalins and substance P in cerebrospinal fluid and plasma of primates","volume":"256","author":"Yaksh TL","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67031301.x"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3673"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.09.005"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000090312"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12335"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529309104005"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(95)02053-5"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(90)90402-R"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00093"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(87)90510-3"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1999.00001.x-i1"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.1992.tb00052.x"},{"issue":"6","key":"e_1_2_13_33_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1365-2036.1999.00002.x-i1","article-title":"Racecadotril versus placebo in the treatment of acute diarrhoea in adults","volume":"13","author":"Hamza H","year":"1999","journal-title":"Aliment Pharmacol Ther"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365529309090255"},{"issue":"6","key":"e_1_2_13_35_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1046\/j.1365-2036.1999.00003.x-i1","article-title":"Comparison of racecadotril and loperamide in adults with acute diarrhoea","volume":"13","author":"Vetel JM","year":"1999","journal-title":"Aliment Pharmacol Ther"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520212495"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0751-3"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i10.1540"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.4236\/ijcm.2014.57052"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.4236\/ijcm.2014.57051"},{"key":"e_1_2_13_41_1","unstructured":"Racecadotril children 30\u00a0mg granules for oral suspension.https:\/\/www.drugs.com\/uk\/racecadotril-children-30mg-granules-for-oral-suspension-leaflet.html. Accessed August 15 2017."},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-309676"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/383819a0"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008382107"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90371-N"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(89)90046-4"},{"issue":"3","key":"e_1_2_13_48_1","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0022-3565(25)24995-3","article-title":"Pharmacological properties of acetorphan, a parenterally active \"enkephalinase\" inhibitor","volume":"237","author":"Lecomte JM","year":"1986","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701882"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(84)90575-2"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)90974-8"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(83)91046-6"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00382-1"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00127a017"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)90186-4"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.05.041"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00091a016"},{"issue":"1","key":"e_1_2_13_58_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0022-3565(25)10959-2","article-title":"Inhibition of the enkephalin\u2010metabolizing enzymes by the first systemically active mixed inhibitor prodrug RB 101 induces potent analgesic responses in mice and rats","volume":"261","author":"Noble F","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(97)00125-5"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.10.004"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13186"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90821-K"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90822-L"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.120"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.08.009"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0934-x"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.11.050"},{"issue":"8","key":"e_1_2_13_68_1","first-page":"1579","article-title":"Treatment of irritable bowel syndrome with Lacteol Fort: a randomized, double\u2010blind, cross\u2010over trial","volume":"91","author":"Halpern GM","year":"1996","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.355"},{"key":"e_1_2_13_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2009.04.017"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.070987"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1521"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301856"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.07.001"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X16663396"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.69"},{"key":"e_1_2_13_77_1","first-page":"771","article-title":"Clinical potential of eluxadoline in the treatment of diarrhea\u2010predominant irritable bowel syndrome","volume":"12","author":"Sobolewska\u2010W\u0142odarczyk A","year":"2016","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1505180"},{"key":"e_1_2_13_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(15)30245-6"},{"key":"e_1_2_13_80_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S23274"},{"key":"e_1_2_13_81_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2010.515209"},{"key":"e_1_2_13_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(01)00782-6"},{"key":"e_1_2_13_83_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.33.6.753"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13526","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nmo.13526","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.13526","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:12:27Z","timestamp":1775308347000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.13526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,14]]},"references-count":82,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/nmo.13526"],"URL":"https:\/\/doi.org\/10.1111\/nmo.13526","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,14]]},"assertion":[{"value":"2018-07-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13526"}}