{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:12:24Z","timestamp":1793211144069,"version":"4.5.0"},"reference-count":209,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA042888; DA048379; DA07242; DA045884; DA046487; DA048379"],"award-info":[{"award-number":["DA042888; DA048379; DA07242; DA045884; DA046487; DA048379"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Mayday Foundation","award":["The Mayday Foundation"],"award-info":[{"award-number":["The Mayday Foundation"]}]},{"name":"The Peter F. McManus Charitable Trust","award":["The Peter F. McManus Charitable Trust"],"award-info":[{"award-number":["The Peter F. McManus Charitable Trust"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Most opioid analgesics used clinically, including morphine and fentanyl, as well as the recreational drug heroin, act primarily through the mu opioid receptor, a class A Rhodopsin-like G protein-coupled receptor (GPCR). The single-copy mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating multiple splice variants or isoforms via a variety of alternative splicing events. These OPRM1 splice variants can be categorized into three major types based on the receptor structure: (1) full-length 7 transmembrane (TM) C-terminal variants; (2) truncated 6TM variants; and (3) single TM variants. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating the distinct actions of various mu opioids. More importantly, the OPRM1 variants can be targeted for development of novel opioid analgesics that are potent against multiple types of pain, but devoid of many side-effects associated with traditional opiates. In this review, we provide an overview of OPRM1 alternative splicing and its functional relevance in opioid pharmacology.<\/jats:p>","DOI":"10.3390\/biom11101525","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:13:32Z","timestamp":1634512412000},"page":"1525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Alternative Pre-mRNA Splicing of the Mu Opioid Receptor Gene, OPRM1: Insight into Complex Mu Opioid Actions"],"prefix":"10.3390","volume":"11","author":[{"given":"Shan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jia","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Abrimian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cartegni","sequence":"additional","affiliation":[{"name":"Department of Chemical Biology, Ernest Mario School of Pharmacy Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-3823","authenticated-orcid":false,"given":"Susruta","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Center for Clinical Pharmacology, University of Health Sciences & Pharmacy and Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Hesketh","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Bekker","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Xian","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"ref_1","first-page":"463","article-title":"Opioid antagonists","volume":"19","author":"Martin","year":"1967","journal-title":"Pharmacol. 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