μ receptor | Opioid receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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μ receptor

Target not currently curated in GtoImmuPdb

Target id: 319

Nomenclature: μ receptor

Family: Opioid receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 400 6q24-q25 OPRM1 opioid receptor mu 1 168
Mouse 7 398 10 A2 Oprm1 opioid receptor, mu 1 105
Rat 7 398 1p11 Oprm1 opioid receptor, mu 1 25,45,150,167,178
Previous and Unofficial Names
Mu receptor | MOP | OP3 | MOPr | opioid receptor, mu 1 | opioid receptor
Database Links
Specialist databases
GPCRDB oprm_human (Hs), oprm_mouse (Mm), oprm_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the mu-opioid receptor bound to a morphinan antagonist
PDB Id:  4DKL
Ligand:  β-FNA
Resolution:  2.8Å
Species:  Mouse
References:  93
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the μ-opioid receptor–Gi protein complex
PDB Id:  6DDF
Ligand:  DAMGO
Resolution:  3.5Å
Species:  Mouse
References:  79
Natural/Endogenous Ligands
dynorphin A-(1-13) {Sp: Human, Mouse, Rat}
dynorphin A {Sp: Human, Mouse, Rat}
dynorphin A-(1-8) {Sp: Human, Mouse, Rat}
dynorphin B {Sp: Human, Mouse, Rat}
endomorphin-1 {Sp: Human}
endomorphin-2 {Sp: Human}
β-endorphin {Sp: Human} , β-endorphin {Sp: Mouse} , β-endorphin {Sp: Rat}
[Leu]enkephalin {Sp: Human, Mouse, Rat}
[Met]enkephalin {Sp: Human, Mouse, Rat}
Comments: β-Endorphin is the highest potency endogenous ligand
Potential endogenous agonists
endomorphin-1, endomorphin-2
Principal endogenous agonists (Human)
β-endorphin (POMC, P01189), [Met]enkephalin (PENK, P01210), [Leu]enkephalin (PENK, P01210)

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]DAMGO Rn Full agonist 9.2 pKd 132
pKd 9.2 (Kd 5.7x10-10 M) [132]
carfentanil Cp Agonist 10.6 pKi 33
pKi 10.6 (Ki 2.4x10-11 M) [33]
Description: Binding affinity in guinea pig whole brain- displacement of [3H]DAGO binding.
(-)-cyclazocine Hs Partial agonist 10.0 pKi 154
pKi 10.0 [154]
butorphanol Hs Partial agonist 9.9 pKi 47
pKi 9.9 (Ki 1.2x10-10 M) [47]
Description: Displacement of [3H]DAMGO from human μ opioid receptor expressed in CHO cells.
sufentanil Hs Full agonist 9.9 pKi 163
pKi 9.9 (Ki 1.38x10-10 M) [163]
etonitazene Hs Full agonist 9.7 pKi 154
pKi 9.7 [154]
hydromorphone Hs Agonist 9.6 pKi 169
pKi 9.6 (Ki 2.8x10-10 M) [169]
ethylketocyclazocine Hs Full agonist 9.5 pKi 154
pKi 9.5 [154]
etorphine Hs Full agonist 9.5 pKi 154
pKi 9.5 [154]
fentanyl Rn Full agonist 9.4 pKi 132
pKi 9.4 [132]
DAMGO Hs Full agonist 9.3 pKi 58,154
pKi 9.3 [58,154]
loperamide Hs Agonist 9.3 pKi 26
pKi 9.3 (Ki 5.3x10-10 M) [26]
(-)-methadone Hs Full agonist 9.2 pKi 154
pKi 9.2 [154]
[Met]enkephalin {Sp: Human, Mouse, Rat} Rn Full agonist 9.2 pKi 132
pKi 9.2 [132]
fentanyl Hs Full agonist 9.2 pKi 154
pKi 9.2 [154]
cebranopadol Hs Agonist 9.1 pKi 88
pKi 9.1 (Ki 7x10-10 M) [88]
Description: Radioligand binding assay
sufentanil Rn Full agonist 9.1 pKi 172
pKi 9.1 (Ki 7.7x10-10 M) [172]
eluxadoline Rn Agonist 9.1 pKi 18
pKi 9.1 (Ki 9x10-10 M) [18]
morphine Hs Full agonist 9.0 pKi 52,154
pKi 9.0 [52,154]
β-endorphin {Sp: Human} Rn Full agonist 9.0 pKi 132
pKi 9.0 [132]
PZM21 Hs Biased agonist 9.0 pKi 94
pKi 9.0 (Ki 1.1x10-9 M) [94]
bilorphin Hs Agonist 9.0 pKi 36
pKi 9.0 (Ki 1.1x10-9 M) [36]
dihydromorphine Hs Full agonist 8.8 pKi 154
pKi 8.8 [154]
dynorphin-(1-11) Hs Full agonist 8.8 pKi 154
pKi 8.8 [154]
normorphine Hs Full agonist 8.8 pKi 154
pKi 8.8 [154]
nalbuphine Hs Agonist 8.8 pKi 169
pKi 8.8 (Ki 1.6x10-9 M) [169]
buprenorphine Hs Partial agonist 8.8 pKi 154
pKi 8.8 [154]
eluxadoline Hs Agonist 8.8 pKi 18
pKi 8.8 (Ki 1.7x10-9 M) [18]
DADLE Hs Full agonist 8.7 pKi 154
pKi 8.7 [154]
DAMGO Rn Full agonist 8.7 pKi 132
pKi 8.7 [132]
hydrocodone Hs Agonist 8.7 pKi 119
pKi 8.7 (Ki 2x10-9 M) [119]
BU08028 Hs Partial agonist 8.7 pKi 74
pKi 8.7 (Ki 2.14x10-9 M) [74]
cebranopadol Rn Agonist 8.6 pKi 88
pKi 8.6 (Ki 2.4x10-9 M) [88]
Description: Radioligand binding assay
dynorphin B {Sp: Human, Mouse, Rat} Hs Full agonist 8.5 pKi 154
pKi 8.5 [154]
endomorphin-2 {Sp: Human} Rn Full agonist 8.5 pKi 177
pKi 8.5 (Ki 3.24x10-9 M) [177]
(-)-pentazocine Hs Partial agonist 8.4 pKi 154
pKi 8.4 [154]
dynorphin A-(1-8) {Sp: Human, Mouse, Rat} Hs Full agonist 8.4 pKi 154
pKi 8.4 [154]
dynorphin A-(1-13) {Sp: Human, Mouse, Rat} Hs Full agonist 8.3 pKi 154
pKi 8.3 [154]
endomorphin-1 {Sp: Human} Hs Full agonist 8.3 pKi 54,177
pKi 8.3 (Ki 5.01x10-9 M) [54,177]
DSLET Hs Full agonist 8.2 pKi 154
pKi 8.2 [154]
PL017 Hs Full agonist 8.2 pKi 23,154
pKi 8.2 [23,154]
[Leu]enkephalin {Sp: Human, Mouse, Rat} Hs Partial agonist 8.1 pKi 154
pKi 8.1 [154]
dynorphin A {Sp: Human, Mouse, Rat} Hs Full agonist 8.1 pKi 154
pKi 8.1 [154]
UFP-512 Hs Agonist 8.0 pKi 162
pKi 8.0 [162]
Description: Measuring displacement of [3H]-diprenorphine in vitro
morphine Rn Partial agonist 7.9 pKi 132
pKi 7.9 [132]
BW373U86 Rn Agonist 7.8 pKi 22
pKi 7.8 (Ki 1.5x10-8 M) [22]
UFP-505 Hs Agonist 7.8 pKi 38-39
pKi 7.8 [38-39]
ADL5747 Hs Agonist 7.7 pKi 84
pKi 7.7 (Ki 1.8x10-8 M) [84]
ADL5859 Hs Agonist 7.5 pKi 83
pKi 7.5 (Ki 3.2x10-8 M) [83]
SCH221510 Hs Agonist 7.2 pKi 161
pKi 7.2 (Ki 6.5x10-8 M) [161]
Description: Radioligand binding assay
SR16835 Hs Agonist 7.1 pKi 155
pKi 7.1 (Ki 7.99x10-8 M) [155]
Description: Radioligand binding assay
codeine Hs Full agonist 6.9 pKi 154
pKi 6.9 [154]
tapentadol Hs Agonist 6.8 pKi 157
pKi 6.8 (Ki 1.6x10-7 M) [157]
oxycodegol Hs Agonist 6.6 pKi 108
pKi 6.6 (Ki 2.37x10-7 M) [108]
Description: Competitive membrane binding assay measuring displacement [3H]naloxone from human μ receptors expressed by CHO cells.
BW373U86 Hs Agonist 6.6 pKi 83
pKi 6.6 (Ki 2.6x10-7 M) [83]
HS665 Hs Agonist 6.3 pKi 145
pKi 6.3 (Ki 5.42x10-7 M) [145]
compound 3 [PMID: 23134120] Hs Agonist 6.1 pKi 145
pKi 6.1 (Ki 8.26x10-7 M) [145]
tramadol Hs Agonist 5.8 pKi 169
pKi 5.8 (Ki 1.6x10-6 M) [169]
Description: Displacement of the mu aginist peptide DAMGO from the mu receptor expressed in CHO cells.
PZM21 Hs Biased agonist 8.3 pEC50 94
pEC50 8.3 (EC50 4.6x10-9 M) [94]
Description: In a Gi/o activation assay.
4F-MT-45 Hs Agonist 6.8 pEC50 8
pEC50 6.8 (EC50 1.7x10-7 M) [8]
Description: β-arrestin2 recruitment assay
2F-MT-45 Hs Agonist 6.7 pEC50 8
pEC50 6.7 (EC50 2x10-7 M) [8]
Description: β-arrestin2 recruitment assay
3F-MT-45 Hs Agonist 6.2 pEC50 8
pEC50 6.2 (EC50 6.1x10-7 M) [8]
Description: β-arrestin2 recruitment assay
MT-45 Hs Agonist 4.6 pEC50 8
pEC50 4.6 (EC50 2.3x10-5 M) [8]
Description: β-arrestin2 recruitment assay
levorphanol Hs Agonist 9.9 pIC50 60
pIC50 9.9 (IC50 1.3x10-10 M) [60]
BU72 Cp Agonist 9.8 pIC50 65
pIC50 9.8 (IC50 1.5x10-10 M) [65]
Description: Measuring displacement of [3H]DAMGO from brain membranes isolated from Hartley guinea pigs.
methadone Hs Agonist 8.4 pIC50 130
pIC50 8.4 (IC50 4.1x10-9 M) [130]
Description: Binding affinity against μ-opioid receptor (human) using [3H]DAMGO radioligand.
pethidine Hs Agonist 6.5 pIC50 130
pIC50 6.5 (IC50 3.15x10-7 M) [130]
AR-M1000390 Hs Agonist 5.4 pIC50 4
pIC50 5.4 (IC50 3.8x10-6 M) [4]
[3H]PL017 Rn Agonist - - 61
[61]
U-47700 Rn Agonist - - 27
[27]
View species-specific agonist tables
Agonist Comments
Discrimination of full or partial agonism is very dependent on the level of receptor expression and on the assay used to monitor agonist effects. Many agents may behave as full agonists or potent partial agonists in cell lines expressing cloned receptors in high concentration, but in other environments they may show only weak agonist activity. The identification of agonist activity in the table is largely based on the ability to stimulate GTPγ35S binding in cell lines expressing cloned human μ receptors. Agents giving 85% or greater stimulation than that given by DAMGO have been characterized as Full Agonists [154].

It is still unclear whether endomorphins are endogenous. Morphine occurs endogenously [129].

We have tagged the μ receptor as the primary drug target for hydrocodone based on this drug having the highest affinity at this receptor compared to the κ and δ receptors [119]. Similarly, we have tagged the μ receptor as the primary target of hydromorphone [169].

Methadone is selective for the μ receptor: comparable IC50s at the κ and δ receptors are 512 and 1090nM respectively [130].

[11C]carfentanil (PubChem CID 449698) binds the human μ receptor with a Ki of 0.07 nM, in a [3H]DAMGO displacement assay [62].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]diprenorphine Mm Antagonist 10.1 pKd 132
pKd 10.1 (Kd 7.94x10-11 M) [132]
[3H]naloxone Rn Antagonist 8.6 – 9.0 pKd 121
pKd 8.6 – 9.0 (Kd 2.8x10-9 – 1x10-9 M) [121]
Description: CHO and BHK cell lines stably expressing the rat μ receptor
naloxonazine Mm Antagonist 10.3 pKi 132
pKi 10.3 [132]
samidorphan Hs Antagonist 10.3 pKi 170
pKi 10.3 (Ki 5.2x10-11 M) [170]
diprenorphine Mm Antagonist 10.1 pKi 132
pKi 10.1 [132]
quadazocine Hs Antagonist 10.0 pKi 154
pKi 10.0 [154]
(-)-bremazocine Hs Antagonist 9.7 pKi 154
pKi 9.7 [154]
CTOP Hs Antagonist 9.7 pKi 132
pKi 9.7 [132]
nalmefene Hs Antagonist 9.5 pKi 154
pKi 9.5 [154]
β-FNA Hs Antagonist 9.5 pKi 154
pKi 9.5 [154]
β-FNA Mm Antagonist 9.5 pKi 132
pKi 9.5 [132]
NFP Hs Antagonist 9.4 pKi 180
pKi 9.4 (Ki 3.6x10-10 M) [180]
Description: In a competitive radioligand membrane binding assay measuring displacement of [3H]naloxone by NFP from μ receptor expressed in CHO cells.
naltrexone Hs Antagonist 9.1 – 9.7 pKi 73,154
pKi 9.1 – 9.7 (Ki 7.1x10-10 – 1.99x10-10 M) [73,154]
GSK1521498 Hs Antagonist 9.4 pKi 73
pKi 9.4 (Ki 4.17x10-10 M) [73]
alvimopan Hs Antagonist 9.3 pKi 82
pKi 9.3 (Ki 4.7x10-10 M) [82]
diprenorphine Hs Antagonist 9.1 pKi 154
pKi 9.1 [154]
levallorphan Hs Antagonist 8.8 – 9.3 pKi 92
pKi 8.8 – 9.3 (Ki 1.69x10-9 – 4.8x10-10 M) [92]
Description: Competition binding assay- the calculated Ki varies depending on the radioligand used.
naloxone Mm Antagonist 9.0 pKi 132
pKi 9.0 [132]
naldemedine Hs Antagonist 8.9 pKi 67
pKi 8.9 (Ki 1.13x10-9 M) [67]
nalorphine Hs Antagonist 8.9 pKi 154
pKi 8.9 [154]
naloxone Hs Antagonist 8.9 pKi 154
pKi 8.9 [154]
BNTX Hs Antagonist 8.8 pKi 154
pKi 8.8 [154]
AT-076 Hs Antagonist 8.8 pKi 154,179
pKi 8.8 (Ki 1.67x10-9 M) [154,179]
Description: Radioligand binding assay
methylnaltrexone Hs Antagonist 8.7 pKi 169
pKi 8.7 (Ki 2x10-9 M) [169]
Description: Displacement of [3H]DAMGO from human μ opioid receptors expressed in CHO cells
CTAP Hs Antagonist 8.6 pKi 23,154
pKi 8.6 [23,154]
naloxone benzoylhydrazone Hs Antagonist 8.2 – 8.7 pKi 154
pKi 8.7 [154]
pKi 8.2 [154]
naltrindole Hs Antagonist 8.2 pKi 154
pKi 8.2 [154]
naltriben Hs Antagonist 7.9 pKi 154
pKi 7.9 [154]
nor-binaltorphimine Hs Antagonist 7.7 pKi 154
pKi 7.7 [154]
LY2456302 Hs Antagonist 7.6 pKi 134
pKi 7.6 (Ki 2.4x10-8 M) [134]
zyklophin Hs Antagonist 5.2 pKi 123
pKi 5.2 (Ki 5.88x10-6 M) [123]
BTRX-335140 Hs Antagonist 7.0 pIC50 55
pIC50 7.0 (IC50 1.1x10-7 M) [55]
View species-specific antagonist tables
Antagonist Comments
β-FNA is an electrophilic affinity label. The pKi reflects both the reversible and irreversible binding components.
CTOP is a good somatostatin receptor (sst receptor) agonist in addition to having antagonist activity at μ opioid receptors; it should never be used in studies of μ receptor function in situations where sst receptors may be involved. CTAP does not activate sst receptors [31].

The μ receptor is tagged as the primary target for the drug levallorphan, since the drug is mainly used for its antagonistic actions as an antidote to opioid overdose. Note that this drug also acts as a partial agonist at the κ receptor.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BMS-986123 Hs Neutral 6.0 pKB 19
pKB 6.0 (KB 1x10-6 M) [19]
BMS-986121 Hs Positive 5.7 pKB 19
pKB 5.7 (KB 2x10-6 M) [19]
BMS-986124 Hs Neutral 5.7 pKB 19
pKB 5.7 (KB 2x10-6 M) [19]
BMS-986122 Hs Positive 5.3 pKB 19
pKB 5.3 (KB 5x10-6 M) [19]
BMS-986187 Rn Positive 7.2 pKi 89
pKi 7.2 (Ki 6.3x10-8 M) In the presence of 10 μM BMS-986187, the affinity of the μ-OR agonist DAMGO was enhanced 11-fold from 724 nM to 63 nM. [89]
BMS-986121 Hs Positive 6.0 pEC50 19
pEC50 6.0 (EC50 1x10-6 M) [19]
BMS-986122 Hs Positive 5.5 pEC50 19
pEC50 5.5 (EC50 3x10-6 M) [19]
View species-specific allosteric modulator tables
Allosteric Modulator Comments
BMS-986123 and BMS-986124 are Silent Allosteric Modulators (SAMs). These compounds neither potentiate nor inhibit the actions of an orthosteric agonist, however they block the actions of the Positive Allosteric Modulators (PAMs).
A number of proteins such as G protein-coupled receptor kinases, β-arrestins and G proteins clearly regulate μ opioid receptor affinities and function. In addition sodium and guanyl nucleotides can modify the functional μ receptor complex and G protein interaction. Also, μ receptors are reported to form heterodimers with other receptors of the OP family or with non-opioid G protein-coupled receptors. Heterodimerisation may alter μ receptor function and/or trafficking [49,53,124].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 16 [PMID: 31498617] Hs Binding 5.4 pKi 131
pKi 5.4 (Ki 3.73x10-6 M) [131]
Description: Receptor binding in a radioligand displacement assay using [3H]DAMGO as tracer.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002438 acute inflammatory response to antigenic stimulus IEA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase stimulation
Adenylate cyclase inhibition
Phospholipase C stimulation
Potassium channel
Calcium channel
Phospholipase A2 stimulation
Phospholipase D stimulation
Other - See Comments
Comments:  The following systems have also been reported to be activated following Gi/Go activation via the μ receptor:
  • Epidermal growth factor receptor transactivation and subsequent mitogen activated protein kinase ERK [12,87]
  • Jun N-terminal kinase (JNK) expression and activity [43,71,142]
  • Signal transducer and activator of transcription 3 (STAT3) [176]
  • Focal adhesion kinase [95]
  • Nuclear Ca2+/calmodulin translocation [164]
  • Phosphatidylinositol-3 kinase expression and activity [71,117].
References:  6,17,20-21,34,46,63,76,107,110,116,120,127-128,133,158,174
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
Comments:  G16 couples to the μ opioid receptor and activates PLC.
References:  64,85
Tissue Distribution
Immune cells: CEM x174 T/B lymphocytes, Raji B cells, CD4+, monocytes/macrophages, neutrophils.
Species:  Human
Technique:  RT-PCR.
References:  32
Skin: dermal and epidermal nerve fibers.
Species:  Human
Technique:  Immunohistochemistry.
References:  146
CNS: caudate putamen, nucleus accumbens, endopiriform nucleus, fundus striati, habenula, amygdaloid nuclei, thalamus, hypothalamus, zona incerta, ventral tegmental area, interpeduncular nucleus, central gray, dentate gyrus, substantia nigra, the superior colliculus.
Species:  Mouse
Technique:  Radioligand binding.
References:  75
Pregnant uterus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  181
CNS: olfactory bulb.
Species:  Rat
Technique:  immunocytochemistry.
References:  139
CNS: cerebral cortex, striatum, hippocampus, locus coeruleus, superficial laminae of the dorsal horn.
Species:  Rat
Technique:  Immunohistochemistry.
References:  5
Gastrointestinal tract.
Species:  Rat
Technique:  Immunohistochemistry.
References:  7
CNS: superficial layers of the dorsal horn.
Species:  Rat
Technique:  immunocytochemistry.
References:  29-30
CNS: striatum, medial habenular nucleus, medial terminal nucleus of the accessory optic tract, interpeduncular nucleus, median raphe nucleus, parabrachial nuclei, locus coeruleus, ambiguous nucleus, nucleus of the solitary tract, and laminae I and II of the medullary and spinal dorsal horns, cerebral cortex, amygdala, thalamus, and hypothalamus.
Species:  Rat
Technique:  Immunohistochemistry.
References:  40
CNS: striatum, layers I and III of the cortex, the pyramidal cell layer of the hippocampal formation, specific nuclei of the thalamus, the pars reticulata of the substantia nigra, the interpeduncular nucleus, and the locus coeruleus.
Species:  Rat
Technique:  Radioligand binding.
References:  149
Accessory optic tract.