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	CHEMBL233 (Hs), CHEMBL2858 (Mm), CHEMBL270 (Rn)
DrugBank Target	P35372 (Hs)
Ensembl Gene	ENSG00000112038 (Hs), ENSMUSG00000000766 (Mm), ENSRNOG00000018191 (Rn)
Entrez Gene	4988 (Hs), 18390 (Mm), 25601 (Rn)
Human Protein Atlas	ENSG00000112038 (Hs)
KEGG Gene	hsa:4988 (Hs), mmu:18390 (Mm), rno:25601 (Rn)
OMIM	600018 (Hs)
Pharos	P35372 (Hs)
RefSeq Nucleotide	NM_000914 (Hs), NM_001039652 (Mm), NM_013071 (Rn)
RefSeq Protein	NP_000905 (Hs), NP_001034741 (Mm), NP_037203 (Rn)
SynPHARM	3941 (in complex with β-FNA)
UniProtKB	P35372 (Hs), P42866 (Mm), P33535 (Rn)
Wikipedia	OPRM1 (Hs)

Selected 3D Structures
	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
	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.