Protein / target

Delta-type opioid receptor

OPRD1P41143Homo sapiensSwiss-Prot
UniProt: P41143Ensembl: ENSG00000116329HGNC: HGNC:8153NCBI Gene: 4985
Clinically validated
Therapeutic maturity
20
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

G protein-coupled enkephalin receptor activity

Primary system

Nervous system

Strongest disease association

Pain

Clinical evidence · score 0.61

Therapeutic maturity

Clinically validated target

20 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

20 approved · 6 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

G protein-coupled receptor that functions as a receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine

Subcellular location

Cell membrane
Domains and Gene Ontology detail (29)

Gene Ontology

  • Caxon terminus
  • Cdendrite membrane
  • Cneuron projection
  • Cneuronal dense core vesicle
  • Cplasma membrane
  • Cpostsynaptic density membrane
  • Cpresynaptic membrane
  • Cspine apparatus
  • Csynaptic vesicle membrane
  • FG protein-coupled enkephalin receptor activity
  • FG protein-coupled opioid receptor activity
  • Fneuropeptide binding

372 aa · 40 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

G protein-coupled signallingUniProt · GOImmune signallingGO · ReactomeSynaptic signallingGOTranscriptional regulationGO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor that functions as a receptor for endogenous enkephalins and f…
  • ·G protein-coupled enkephalin receptor activity
  • ·G protein-coupled opioid receptor activity
  • ·G protein-coupled opioid receptor signaling pathway

Immune signalling

  • ·immune response
  • ·Interleukin-4 and Interleukin-13 signaling

Synaptic signalling

  • ·postsynaptic density membrane
  • ·presynaptic membrane

Transcriptional regulation

  • ·negative regulation of gene expression
View underlying pathways (3)
Peptide ligand-binding receptors
G alpha (i) signalling events
Interleukin-4 and Interleukin-13 signaling

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

GNAI1PENKPDYNOPRM1POMCKNG1GNAI2GNAI3PNOCGPRASP1OPRD1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

1

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Naltrexone
ApprovedAntagonist

Opioid receptors; mu/kappa/delta antagonist

Appears in clinical studies involving alcohol dependence, Overweight, Obesity, Borderline personality disorder

Acts on a complex — shared with OPRK1, OPRM1 · 1 of 3 recorded protein targets — narrow recorded profile

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

Pain1.00

Clinical · overall 0.61

alcohol dependence0.99

Clinical · overall 0.60

migraine disorder0.97

Clinical · overall 0.60

opiate dependence0.97

Clinical · overall 0.60

drug dependence0.96

Clinical · overall 0.59

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Obesity0.57

Clinical

major depressive disorder0.56

Clinical

schizophrenia0.51

Clinical

Overweight0.50

Clinical

bipolar I disorder0.49

Clinical

Show all associations
Pain0.61
alcohol dependence0.60
migraine disorder0.60
opiate dependence0.60
drug dependence0.59
Obesity0.57
major depressive disorder0.56
schizophrenia0.51
Overweight0.50
bipolar I disorder0.49

Open Targets ranks 248 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 26 total

NALOXONE HYDROCHLORIDEApproval

Pain · major depressive disorder · septic shock

NALMEFENE HYDROCHLORIDE DIHYDRATEApproval

alcohol dependence

NALBUPHINEApproval

Pain · prurigo nodularis · post operative nausea and vomiting

SAMIDORPHAN L-MALATEApproval

schizophrenia · bipolar I disorder

DEXTROMORAMIDEApproval

Pain

HYDROCODONE BITARTRATEApproval

Pain · drug dependence · Chronic pain

ONDELOPRANApproval

alcohol dependence

OXYMORPHONE HYDROCHLORIDEApproval

Pain

AXOMADOLPhase 2

Back pain · Low back pain

CODEINE SULFATEApproval

drug dependence · Pain

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Small Molecule Binder

Safety liabilities

heroin dependenceseizureincreased cardiac outputcardiovascular effectseuphoriaincreased contractilitycardiovascular effectsincreased blood pressuredysphoriaconvulsionsincreased cardiac contractilityconvulsion

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Pharmacogenetic Investigation of NaltrexonePHASE2

COMPLETED · via Naltrexone · NCT00270231

Low Dose Naltrexone (LDN) Immune MonitoringNA

COMPLETED · via Naltrexone · NCT02107014

HIV Risk Reduction and Drug Abuse Treatment in IranPHASE2

WITHDRAWN · via Naltrexone · NCT00398008

Low Dose Naltrexone (LDN) for the Treatment of Chronic Neuropathic Pain in Patients With Human Immunodeficiency Virus (HIV), a Prospective, Pragmatic, Open Label Clinical TrialPHASE4

RECRUITING · via Naltrexone · NCT05537935

Dopamine D2/3- and μ-opioid Receptor Antagonists Reduce Cue-induced Reward Responding and Reward Impulsivity in Healthy VolunteersNA

COMPLETED · via Naltrexone · NCT02557984

Adherence to HIV Therapy in Heroin Addicts: Oral vs. Extended Release NaltrexonePHASE2

COMPLETED · via Naltrexone · NCT01101815

Show remaining trials (24)
A Randomized, Double-Blinded Clinical Trial to Evaluate the Effectiveness of Naltrexone in Improving Nonsuicidal Self-Injurious BehaviorNA

NOT_YET_RECRUITING · via Naltrexone · NCT07641283

Naltrexone and Nicotine Replacement Effects on Cue Reactivity of SmokersNA

COMPLETED · via Naltrexone · NCT00018213

The Evaluation of Safety and Tolerance of Commercially Available Naltrexone Administered Daily - Assessment for CBRN OperationsPHASE1

COMPLETED · via Naltrexone · NCT03879460

Behavioral/Pharmacological Treatments for Alcohol-Nicotine DependencePHASE4

COMPLETED · via Naltrexone · NCT00000447

Neuropharmacological Basis of Social Connection: The Role of OpioidsNA

COMPLETED · via Naltrexone · NCT01672723

The Use of Naltrexone Hydrochloride to Promote Healing in Patients With Resistant Non-infectious Corneal UlcerNA

COMPLETED · via Naltrexone · NCT05924893

Randomized, Double-blind, Placebo-controlled Study of Naltrexone for Impulse Control Disorders in Parkinson's DiseasePHASE4

COMPLETED · via Naltrexone · NCT01052831

Combined Treatment for Cocaine-Alcohol DependencePHASE2

COMPLETED · via Naltrexone · NCT00218569

Naltrexone for At-Risk and Problem Drinking in Smoking Cessation TreatmentPHASE2

COMPLETED · via Naltrexone · NCT00938886

Behavioral Naltrexone Therapy (BNT) for Promoting Adherence to Oral Naltrexone (BNT-oral) vs Extended Release Injectable Depot Naltrexone (Depot-BNT); a Randomized TrialPHASE3

COMPLETED · via Naltrexone · NCT00577408

Opiate Dependence: Combined Naltrexone/Behavior TherapyPHASE2

COMPLETED · via Naltrexone · NCT00238914

Nalrexone Facilitated Discontinuation of BuprenorphinePHASE1/PHASE2

COMPLETED · via Naltrexone · NCT01895036

A Clinical Trial to Assess a Single Dose of Low-Dose Naltrexone and Acetaminophen Combination and Its Components in the Acute Treatment of MigrainePHASE2

COMPLETED · via Naltrexone · NCT03061734

Naltrexone, Craving, and Drinking: Ecological AssessmentPHASE4

COMPLETED · via Naltrexone · NCT00006203

Phase II Study of Naltrexone for the Treatment of Hormone-Refractory, Metastatic Breast CancerPHASE2

TERMINATED · via Naltrexone · NCT00379197

Low-Dose Naltrexone for the Treatment of Painful Diabetic Neuropathy, a Small, Randomized, Double-blind, Placebo-controlled Crossover TrialPHASE2

RECRUITING · via Naltrexone · NCT04678895

Low Dose Naltrexone for Chronic Pain in Osteoarthritis and Inflammatory ArthritisPHASE2

WITHDRAWN · via Naltrexone · NCT04115020

Naltrexone and CBT for Problem-Drinking MSMPHASE3

UNKNOWN · via Naltrexone · NCT01115894

Low Dose Naltrexone (LDN) Therapy for Complex Regional Pain Syndrome (CRPS): A Feasibility StudyPHASE4

ENROLLING_BY_INVITATION · via Naltrexone · NCT06306157

A Single-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of Topical Naltrexone Ophthalmic Solution on the Signs and Symptoms of Dry Eye in Diabetic SubjectsPHASE2

COMPLETED · via Naltrexone · NCT03660475

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study Evaluating the Efficacy and Safety of Naltrexone Hydrochloride Implant for the Treatment of Alcohol Use DisorderPHASE3

NOT_YET_RECRUITING · via Naltrexone · NCT07433413

Naltrexone and SSRI Therapy for Alcohol Dependence in Alaska NativesPHASE2

COMPLETED · via Naltrexone · NCT00000451

Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19PHASE2

TERMINATED · via Naltrexone · NCT04365985

Neurobiology of Opioid Dependence: 5PHASE2

WITHDRAWN · via Naltrexone · NCT00000196

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

PainModerately supported
0.75
agreement 0.58–0.91
Clinical100%

Open Targets aggregate 0.61 · 1 independent evidence family

alcohol dependenceModerately supported
0.74
agreement 0.59–0.90
Clinical98%Literature2%

Open Targets aggregate 0.60 · 2 independent evidence families

migraine disorderModerately supported
0.74
agreement 0.58–0.89
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

opiate dependenceModerately supported
0.74
agreement 0.58–0.89
Clinical97%Literature3%

Open Targets aggregate 0.60 · 2 independent evidence families

drug dependenceModerately supported
0.72
agreement 0.57–0.88
Clinical97%Literature3%

Open Targets aggregate 0.59 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

8

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2023-09-26
    Naltrexone/bupropion for binge-eating disorder: A randomized, double-blind, placebo-controlled trial.

    Obesity (Silver Spring, Md.) · 2023 · 40 citations · Europe PMC · via Naltrexone

  2. New publication2016-10-01
    Randomized, proof-of-concept trial of low dose naltrexone for patients with breakthrough symptoms of major depressive disorder on antidepressants.

    Journal of affective disorders · 2017 · 41 citations · Europe PMC · via Naltrexone

  3. New publication2015-05-01
    Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial.

    JAMA psychiatry · 2015 · 87 citations · Europe PMC · via Naltrexone

  4. New publication2014-07-18
    Naltrexone for impulse control disorders in Parkinson disease: a placebo-controlled study.

    Neurology · 2014 · 78 citations · Europe PMC · via Naltrexone

  5. New publication2013-04-01
    Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study.

    Journal of clinical gastroenterology · 2013 · 38 citations · Europe PMC · via Naltrexone

  6. New publication2011-03-31
    Gabapentin combined with naltrexone for the treatment of alcohol dependence.

    The American journal of psychiatry · 2011 · 95 citations · Europe PMC · via Naltrexone

  7. New publication2010-06-12
    Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial.

    Drug and alcohol dependence · 2010 · 35 citations · Europe PMC · via Naltrexone

  8. New publication2006-09-08
    Association of OPRM1 A118G variant with the relative reinforcing value of nicotine.

    Psychopharmacology · 2006 · 95 citations · Europe PMC · via Naltrexone

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.