OPRM1 opioid receptor mu 1
ENSG00000112038 · protein coding · Open Targets profile
Receptor for endogenous opioids such as beta-endorphin and endomorphin (PubMed:10529478, PubMed:12589820, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone (PubMed:10529478, PubMed:10836142, PubMed:12589820, PubMed:19300905, PubMed:7891175, PubMed:7905839, PubMed:7957926, PubMed:9689128). Also activated by enkephalin peptides, such as Met-enkephalin or Met-enkephalin-Arg-Phe, with higher affinity for Met-enkephalin-Arg-Phe (By similarity). Agonist binding to the receptor induces coupling to an inactive GDP- bound heterotrimeric G protein complex and subsequent exchange of GDP for GTP in the G protein alpha subunit leading to dissociation of the G protein complex with the free GTP-bound G protein alpha and the G protein beta-gamma dimer activating downstream cellular effectors (PubMed:7905839). The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extent to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15 (PubMed:12068084). They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF- kappa-B (By similarity). Also couples to adenylate cyclase stimulatory G alpha proteins (By similarity). The selective temporal coupling to G proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4 (By similarity). Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization (By similarity). Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G protein thus terminating signal transduction (By similarity). The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins (By similarity). The activation of the ERK pathway occurs either in a G protein-dependent or a beta-arrestin- dependent manner and is regulated by agonist-specific receptor phosphorylation (By similarity). Acts as a class A G protein-coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling (By similarity). Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G protein coupling (By similarity). Endogenous ligands induce rapid desensitization, endocytosis and recycling (By similarity). Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties (By similarity). {ECO:0000250|UniProtKB:P33535, ECO:0000269|PubMed:10529478, ECO:0000269|PubMed:12068084, ECO:0000269|PubMed:12589820, ECO:0000269|PubMed:7891175, ECO:0000269|PubMed:7905839, ECO:0000269|PubMed:7957926, ECO:0000269|PubMed:9689128, ECO:0000303|PubMed:10836142, ECO:0000303|PubMed:19300905}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Ligand, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.849120020866394 (upper bound 1.1710000038146973). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against OPRM1 (meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadone), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Senthilkumar SadhasivamUniversity of Pittsburgh · 2 of 3 trials Phase 2+
- Aaron FoxMontefiore Medical Center · 2 of 2 trials Phase 2+
- Adam BisagaNew York State Psychiatric Institute · 2 of 2 trials Phase 2+
- Gulraj S ChawlaIndiana University · 2 of 2 trials Phase 2+
- James R LangabeerThe University of Texas Health Science Center, Houston · 2 of 2 trials Phase 2+
- Kathryn HawkYale University · 2 of 2 trials Phase 2+
- Krishnan RamanujanMayo Clinic · 2 of 2 trials Phase 2+
- Li LiUniversity of Alabama at Birmingham · 2 of 2 trials Phase 2+
- Lisa M. EinhornDuke University · 2 of 2 trials Phase 2+
- Luana CollocaUniversity of Maryland Baltimore School of Nursing · 2 of 2 trials Phase 2+
- Man Kin WongChinese University of Hong Kong · 2 of 2 trials Phase 2+
- Sandeep NayakJohns Hopkins University · 2 of 2 trials Phase 2+
- Aaron D FoxAlbert Einstein College of Medicine · 1 of 2 trials Phase 2+
- Caitlin E SmithMedical University of South Carolina · 1 of 2 trials Phase 2+
- Jessica MoeUniversity of British Columbia · 1 of 2 trials Phase 2+
Registry trials of meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadone updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 376 of 387 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 13 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
268 trials of drugs against OPRM1 were stopped early; 18 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadone, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 268.
- withdrawn · 2026-09-08 · New York State Psychiatric Institute · Buprenorphine SL“Due to a federally mandated, institution-wide pause in research activities under the institution's Federal Wide Assurance (FWA) that occurred during the timeline for this study, recruitment was never initiated and no participants were enrolled.”
- terminated · 2026-09-08 · Friends Research Institute, Inc. · matched by the registry's drug synonyms“Loss of sponsor funding”
- withdrawn · 2026-08-17 · Wake Forest University Health Sciences · Single dose of methadone, Split dose of methadone, Balanced split dose of methadone“loss of funding”
- terminated · 2026-07-31 · Boehringer Ingelheim · matched by the registry's drug synonyms“Sponsor decision”
- terminated · 2026-07-29 · Leiden University Medical Center · Naloxone Hydrochloride“Recruitment of chronic opioid users was substantially lower than anticipated despite extensive recruitment efforts; the study was therefore closed before reaching the planned sample size.”
- withdrawn · 2026-07-28 · Icahn School of Medicine at Mount Sinai · Buprenorphine“Enrollment was discontinued after limited accrual prevented feasible completion of the trial.”
- terminated · 2026-07-10 · Stanford University · matched by the registry's drug synonyms“Study terminated due to early participant drop out”
- terminated · 2026-06-29 · Yale University · matched by the registry's drug synonyms“lack of eligible participants”
- terminated · 2026-06-23 · University of Florida · Standard dosing of methadone, Aliquots of methadone titrated to apnea“PI left institution.”
- terminated · 2026-06-04 · University of California, Irvine · Remifentanil +ultra-low dose naloxone“Study terminated early due to low enrollment. Only 8 participants enrolled out of the target 105.”
- terminated · 2026-06-02 · National Institute on Drug Abuse (NIDA) · matched by the registry's drug synonyms“Drug availability”
- terminated · 2026-05-19 · Albert Einstein College of Medicine · naloxone“Protocol was terminated due to enrollment + feasibility issues. Aim 2 not conducted. Aims 1 + 3 were conducted in part. During Aim 3 the IRB requested that the study be transitioned under a new protocol (2018-9208) in order to simplify reporting.”
- terminated · 2026-05-08 · Theresa Jacob, PhD, MPH · Buprenorphine/Naloxone“Principal Investigator is no longer at this site”
- terminated · 2026-05-08 · Montefiore Medical Center · matched by the registry's drug synonyms“Difficulty recruiting and enrolling participants”
- terminated · 2026-04-07 · University of Pennsylvania · Methadone, Buprenorphine/naloxone“Funding not renewed”
- withdrawn · 2026-04-02 · New York State Psychiatric Institute · matched by the registry's drug synonyms“The U.S. Department of Health and Human Services Office of Human Research Protections issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023.”
- suspended · 2026-03-13 · Mauro Manconi · D-methadone“budget issues”
- withdrawn · 2026-03-09 · Universidad Europea de Canarias · matched by the registry's drug synonyms“Study not initiated prior to enrollment.”
- withdrawn · 2026-03-09 · University of North Carolina, Chapel Hill · matched by the registry's drug synonyms“Inability to recruit participants”
- withdrawn · 2026-02-23 · Johns Hopkins University · matched by the registry's drug synonyms“This study was de-prioritized in favor of the similar BIPOD-Out protocol due to a combination of practical considerations and expense. There are currently no plans to initiate this protocol.”
- withdrawn · 2026-02-18 · Rhode Island Hospital · matched by the registry's drug synonyms“The study was initiated but no participants were enrolled.”
- suspended · 2026-02-03 · Friends Research Institute, Inc. · Buprenorphine/Naloxone“Unable to recruit from study sites.”
- terminated · 2026-01-21 · National Cancer Institute (NCI) · Loperamide“This protocol was terminated prematurely because the prior principal investigator departed the Institute without treating any participants.”
- withdrawn · 2026-01-15 · Massachusetts General Hospital · Buprenorphine/Naloxone“lack of funding”
- terminated · 2026-01-07 · University of Alabama at Birmingham · matched by the registry's drug synonyms“No funding for this project”
Paediatric incentives and obligations for OPRM1's drugs
For meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadone: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · OPRM1 is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-000325-PIP01-08-M11 (tapentadol hydrochloride, Treatment of chronic pain): PM: decision on the application for modification of an agreed PIP, 1 Dec 2023; EMEA-001567-PIP01-13-M03 (naloxone (hydrochloride), Treatment of opioid-induced constipation): PM: decision on the application for modification of an agreed PIP, 7 May 2018; EMEA-000018-PIP01-07-M14 (tapentadol hydrochloride, Treatment of acute pain): PM: decision on the application for modification of an agreed PIP, 1 Dec 2017; EMEA-002099-PIP01-16 (buprenorphine hydrochloride, Treatment of opioid dependence): W: decision granting a waiver in all age groups for all conditions or indications, 7 Jun 2017; +8 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: no · No EU orphan designation names meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadoneRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Suboxone: withdrawn since 26 Sept 2006; Moventig: authorised since 7 Dec 2014; Zubsolv: authorised since 10 Nov 2017; Sixmo: withdrawn since 19 Jun 2019; +3 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadoneRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 161 interventional studies of meperidine, naloxegol oxalate, levallorphan, tapentadol, levorphanol, loperamide, oxycodone terephthalate, buprenorphine, anileridine, naloxone, ondelopran, methadone include patients under 18; 30 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 87 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.