{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T16:41:32Z","timestamp":1784392892276,"version":"3.55.0"},"reference-count":212,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["FK_138389"],"award-info":[{"award-number":["FK_138389"]}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["TKP 2021 EGA-25"],"award-info":[{"award-number":["TKP 2021 EGA-25"]}]},{"name":"Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Neurology Thematic Programme of Semmelweis University","award":["FK_138389"],"award-info":[{"award-number":["FK_138389"]}]},{"name":"Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Neurology Thematic Programme of Semmelweis University","award":["TKP 2021 EGA-25"],"award-info":[{"award-number":["TKP 2021 EGA-25"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Opioid receptor agonists, particularly those that activate \u00b5-opioid receptors (MORs), are essential analgesic agents for acute or chronic mild to severe pain treatment. However, their use has raised concerns including, among others, intestinal dysbiosis. In addition, growing data on constipation-evoked intestinal dysbiosis have been reported. Opioid-induced constipation (OIC) creates an obstacle to continuing treatment with opioid analgesics. When non-opioid therapies fail to overcome the OIC, opioid antagonists with peripheral, fast first-pass metabolism, and gastrointestinal localized effects remain the drug of choice for OIC, which are discussed here. At first glance, their use seems to only be restricted to constipation, however, recent data on OIC-related dysbiosis and its contribution to the appearance of several opioid side effects has garnered a great of attention from researchers. Peripheral MORs have also been considered as a future target for opioid analgesics with limited central side effects. The properties of MOR antagonists counteracting OIC, and with limited influence on central and possibly peripheral MOR-mediated antinociception, will be highlighted. A new concept is also proposed for developing gut-selective MOR antagonists to treat or restore OIC while keeping peripheral antinociception unaffected. The impact of opioid antagonists on OIC in relation to changes in the gut microbiome is included.<\/jats:p>","DOI":"10.3390\/molecules28237766","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T11:19:46Z","timestamp":1700824786000},"page":"7766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Insights into the Current and Possible Future Use of Opioid Antagonists in Relation to Opioid-Induced Constipation and Dysbiosis"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5635-2273","authenticated-orcid":false,"given":"Nariman","family":"Essmat","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1445 Budapest, Hungary"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-6292","authenticated-orcid":false,"given":"D\u00e1vid \u00c1rp\u00e1d","family":"Kar\u00e1di","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1445 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Z\u00e1dor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1445 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7252-0422","authenticated-orcid":false,"given":"Korn\u00e9l","family":"Kir\u00e1ly","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1445 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"F\u00fcrst","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1445 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8488-3266","authenticated-orcid":false,"given":"Mahmoud","family":"Al-Khrasani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyv\u00e1rad t\u00e9r 4, H-1445 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"861","DOI":"10.4103\/0019-5049.193696","article-title":"The isolation of morphine by serturner","volume":"60","author":"Krishnamurti","year":"2016","journal-title":"Indian J. 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