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M2 receptor

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Target not currently curated in GtoImmuPdb

Target id: 14

Nomenclature: M2 receptor

Family: Acetylcholine receptors (muscarinic)

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 466 7q33 CHRM2 cholinergic receptor muscarinic 2 2,9-10,97,148
Mouse 7 466 6 B1 Chrm2 cholinergic receptor, muscarinic 2, cardiac 77
Rat 7 466 4q22 Chrm2 cholinergic receptor, muscarinic 2 127
Previous and Unofficial Names Click here for help
M2 muscarinic acetylcholine receptor | AChR M2 | Chrm-2 | cholinergic receptor, muscarinic 2 | cholinergic receptor | cholinergic receptor, muscarinic 2, cardiac
Database Links Click here for help
Specialist databases
GPCRDB acm2_human (Hs), acm2_mouse (Mm), acm2_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 Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist
PDB Id:  3UON
Ligand:  3-quinuclidinyl-benzilate
Resolution:  3.0Å
Species:  Human
References:  44
Image of receptor 3D structure from RCSB PDB
Description:  Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist iperoxo
PDB Id:  4MQS
Ligand:  iperoxo
Resolution:  3.5Å
Species:  Human
References:  63
Image of receptor 3D structure from RCSB PDB
Description:  Structure of active human M2 muscarinic acetylcholine receptor bound to the agonist iperoxo and allosteric modulator LY2119620
PDB Id:  4MQT
Ligand:  LY2119620
Resolution:  3.7Å
Species:  Human
References:  63
Natural/Endogenous Ligands Click here for help
acetylcholine

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]acetylcholine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Agonist 8.8 pKd 69
pKd 8.8 [69]
[3H]oxotremorine-M Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 pKd 5
pKd 8.7 [5]
NNC 11-1585 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 10.1 pKi 22
pKi 10.1 [22]
NNC 11-1607 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.2 pKi 22
pKi 8.2 [22]
pentylthio-TZTP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.9 pKi 57
pKi 7.9 [57]
methacholine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Agonist 7.2 pKi 95
pKi 7.2 (Ki 5.9x10-8 M) [95]
NNC 11-1314 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.2 pKi 22
pKi 7.2 [22]
xanomeline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.9 – 7.4 pKi 135,142
pKi 6.9 – 7.4 [135,142]
oxotremorine Small molecule or natural product Click here for species-specific activity table Rn Full agonist 6.5 pKi 62
pKi 6.5 [62]
acetylcholine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 6.4 pKi 62
pKi 6.4 [62]
cevimeline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.1 pKi 75
pKi 6.1 (Ki 8.54x10-7 M) [75]
Description: Displacement of [3H]QNB from cloned receptor.
oxotremorine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.0 – 6.6 pKi 57,62
pKi 5.0 – 6.6 [57,62]
arecaidine propargyl ester Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.7 pKi 57
pKi 5.7 [57]
carbachol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 5.7 pKi 62
pKi 5.7 [62]
acetylcholine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 4.3 – 6.5 pKi 21,57,62,68
pKi 4.3 – 6.5 [21,57,62,68]
McN-A-343 Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 4.7 – 6.0 pKi 66
pKi 4.7 – 6.0 [66]
arecoline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 pKi 57
pKi 5.2 [57]
carbachol Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 4.2 – 5.7 pKi 21,57,62
pKi 4.2 – 5.7 [21,57,62]
methylfurmethide Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 pKi 57
pKi 4.9 [57]
oxotremorine-M Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 pKi 57
pKi 4.9 [57]
pilocarpine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Partial agonist 4.9 pKi 57
pKi 4.9 [57]
furtrethonium Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.5 pKi 57
pKi 4.5 [57]
bethanechol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 4.0 pKi 57
pKi 4.0 [57]
iperoxo Small molecule or natural product Ligand has a PDB structure Hs Full agonist 9.8 pEC50 106
pEC50 9.8 [106]
(+)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 – 6.4 pEC50 32,43
pEC50 6.2 – 6.4 [32,43]
(-)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.6 – 5.7 pEC50 32,43
pEC50 5.6 – 5.7 [32,43]
[18F]FP-TZTP Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Full agonist - - 56
[56]
View species-specific agonist tables
Agonist Comments
The binding data for McN-A-343 [66] is found on rat heart.
Please consult references [12,70,102,134,141] for further details of the activity of some of the ligands in this list.
Pilocarpine has been found to be a partial agonist [70,141] and a full agonist [134] at the M2 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist >6.3 pA2 93
pA2 >6.3 [93]
[3H]QNB Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.1 – 10.6 pKd 97
pKd 10.1 – 10.6 (Kd 7.94x10-11 – 2.51x10-11 M) [97]
[3H]tiotropium Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 10.3 pKd 104
pKd 10.3 [104]
[3H]N-methyl scopolamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.3 – 9.9 pKd 19,21,49,57-59,61,68,134
pKd 9.3 – 9.9 (Kd 5.2x10-10 – 1.4x10-10 M) [19,21,49,57-59,61,68,134]
[3H]clidinium Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.6 pKd 62
pKd 9.6 [62]
[3H]N-methyl scopolamine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Rn Antagonist 9.5 pKd 115
pKd 9.5 [115]
[3H]clidinium Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.5 pKd 62
pKd 9.5 [62]
[3H]4NMPB Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.4 pKd 115
pKd 9.4 [115]
[3H]AF DX-384 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 8.7 pKd 84
pKd 8.7 [84]
biperiden Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.2 pKd 8
pKd 8.2 (Kd 6.3x10-9 M) [8]
Cy3B-telenzepine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Hs Antagonist 10.4 pKi 89
pKi 10.4 [89]
tiotropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.9 pKi 28
pKi 9.9 [28]
umeclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.8 pKi 65,104
pKi 9.8 (Ki 1.5x10-10 M) [65,104]
tripitramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 76
pKi 9.6 [76]
revefenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.5 pKi 48
pKi 9.5 (Ki 3.02x10-10 M) [48]
Description: Determined from a radioligand binding assay using membranes from CHO‐K1 cells expressing the hM2 receptor, and displacement of [3H]NMS tracer.
propantheline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.5 pKi 51
pKi 9.5 [51]
THRX160209 Small molecule or natural product Hs Antagonist 9.5 pKi 116
pKi 9.5 [116]
mepenzolic acid Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.2 pKi 143
pKi 9.2 (Ki 6.8x10-10 M) [143]
atropine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 9.0 – 9.1 pKi 60,62
pKi 9.0 – 9.1 [60,62]
dexetimide Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 8.9 pKi 62
pKi 8.9 [62]
ipratropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.8 pKi 49
pKi 8.8 [49]
dexetimide Small molecule or natural product Approved drug Rn Antagonist 8.8 pKi 62
pKi 8.8 [62]
Alexa-488-telenzepine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Hs Antagonist 8.8 pKi 89
pKi 8.8 [89]
scopolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.7 pKi 51
pKi 8.7 [51]
SCH 57790 Small molecule or natural product Hs Antagonist 8.6 pKi 64
pKi 8.6 [64]
AE9C90CB Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 112
pKi 8.6 [112]
benzatropine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Antagonist 8.6 pKi 90
pKi 8.6 (Ki 2.6x10-9 M) [90]
Description: Displacement binding assay using homogenised rat caudate putamen.
atropine Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.8 – 9.2 pKi 13,21,49,51,62,88,97
pKi 7.8 – 9.2 [13,21,49,51,62,88,97]
tolterodine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inverse agonist 8.4 – 8.6 pKi 41,88,112
pKi 8.4 – 8.6 [41,88,112]
AQ-RA 741 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 30,41
pKi 8.4 [30,41]
4-DAMP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.3 pKi 62
pKi 8.3 [62]
4-DAMP Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.2 pKi 60,62
pKi 8.2 [60,62]
AFDX384 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 30
pKi 8.2 [30]
himbacine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.4 pKi 30,59,62,83
pKi 7.9 – 8.4 [30,59,62,83]
ethopropazine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.1 pKi 14
pKi 8.1 (Ki 7.2x10-9 M) [14]
Description: Displacement of [H]QNB binding in rat hindbrain brain homogenate.
amitriptyline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.9 pKi 114
pKi 7.9 (Ki 1.18x10-8 M) [114]
oxybutynin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inverse agonist 7.9 pKi 27
pKi 7.9 (Ki 1.175x10-8 M) [27]
himbacine Small molecule or natural product Rn Antagonist 7.9 pKi 62
pKi 7.9 [62]
oxybutynin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.7 – 8.1 pKi 52,112
pKi 7.7 – 8.1 [52,112]
methoctramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 – 8.4 pKi 13,30,34,47,62,88
pKi 7.3 – 8.4 [13,30,34,47,62,88]
hexocyclium Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.6 pKi 13
pKi 7.6 [13]
(S)-dimetindene Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 7.5 pKi 17
pKi 7.5 (Ki 3.02x10-8 M) [17]
Description: Binding to hM2 receptors expressed in CHO cells.
silahexocyclium Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 pKi 13
pKi 7.5 [13]
UH-AH 37 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 – 7.4 pKi 41,140
pKi 7.3 – 7.4 [41,140]
darifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inverse agonist 7.0 – 7.6 pKi 41,47,49,52,88,112
pKi 7.0 – 7.6 [41,47,49,52,88,112]
methoctramine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.3 pKi 62
pKi 7.3 [62]
solifenacin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.9 – 7.1 pKi 52,112
pKi 6.9 – 7.1 [52,112]
dosulepin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.0 pKi 114
pKi 7.0 (Ki 1.09x10-7 M) [114]
otenzepad Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 7.2 pKi 13,62
pKi 6.7 – 7.2 [13,62]
imipramine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.9 pKi 62
pKi 6.9 [62]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.7 – 6.8 pKi 60,62
pKi 6.7 – 6.8 [60,62]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 6.8 pKi 13,34,62
pKi 6.6 – 6.8 [13,34,62]
hexahydrodifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 pKi 13
pKi 6.7 [13]
dicyclomine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.6 pKi 13
pKi 6.6 [13]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 5.3 – 7.4 pKi 60,62,115
pKi 5.3 – 7.4 [60,62,115]
p-F-HHSiD Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 – 6.6 pKi 34,51
pKi 6.1 – 6.6 [34,51]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.0 – 6.7 pKi 13,30,47,51,59,62,88,140
pKi 6.0 – 6.7 [13,30,47,51,59,62,88,140]
VU0255035 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 110
pKi 6.2 [110]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist <6.0 pKi 59
pKi <6.0 [59]
otenzepad Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.6 – 7.3 pKi 60,62,115
pKi 4.6 – 7.3 [60,62,115]
lithocholylcholine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.4 pKi 21
pKi 5.4 [21]
guanylpirenzepine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.3 pKi 133
pKi 5.3 [133]
muscarinic toxin 7 Peptide Click here for species-specific activity table Hs Antagonist <5.0 pKi 91
pKi <5.0 [91]
levetimide Small molecule or natural product Hs Antagonist 5.0 pKi 62
pKi 5.0 [62]
levetimide Small molecule or natural product Rn Antagonist 4.8 pKi 62
pKi 4.8 [62]
ML381 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <4.5 pKi 39
pKi <4.5 (Ki >3x10-5 M) [39]
aclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.8 pIC50 99
pIC50 9.8 (IC50 1.7x10-10 M) [99]
glycopyrrolate Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.3 pIC50 119
pIC50 9.3 (IC50 5.01x10-10 M) [119]
Description: Assay uses glycopyrronium bromide
solifenacin Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.2 pIC50 98
pIC50 6.2 (IC50 5.73x10-7 M) [98]
View species-specific antagonist tables
Antagonist Comments
Dexetimide is the optical isomer of levetimide [62].

Biperiden is an approved drug antagonist of muscarinic acetylcholine receptors. We have tagged the M1 subtype as the drug's primary target as affinity is 10-fold higher at this receptor subtype [8].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]dimethyl-W84 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Positive 8.5 pKd 126
pKd 8.5 [126]
C7/3-phth Small molecule or natural product Hs Negative 7.1 pKd 23
pKd 7.1 [23]
W-84 Small molecule or natural product Hs Negative 6.0 – 7.5 pKd 86,126
pKd 6.0 – 7.5 [86,126]
alcuronium Small molecule or natural product Click here for species-specific activity table Hs Negative 6.1 – 6.9 pKd 57,126
pKd 6.1 – 6.9 [57,126]
gallamine Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Negative 5.9 – 6.3 pKd 24,68
pKd 5.9 – 6.3 [24,68]
WIN 51,708 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.9 pKd 73
pKd 5.9 [73]
KT 5823 Small molecule or natural product Click here for species-specific activity table Hs Positive 5.7 pKd 72
pKd 5.7 [72]
LY2119620 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 5.7 pKd 26,63
pKd 5.7 [26,63]
WIN 62,577 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.3 pKd 73
pKd 5.3 [73]
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 5.1 pKd 72
pKd 5.1 [72]
vincamine Small molecule or natural product Click here for species-specific activity table Hs Neutral 5.1 pKd 57
pKd 5.1 [57]
Gö 7874 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.0 pKd 72
pKd 5.0 [72]
strychnine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 4.9 – 5.0 pKd 57,68,126
pKd 4.9 – 5.0 [57,68,126]
N-benzyl brucine Small molecule or natural product Click here for species-specific activity table Hs Negative 4.8 pKd 71
pKd 4.8 [71]
N-benzyl brucine Small molecule or natural product Click here for species-specific activity table Hs Positive 4.8 pKd 71
pKd 4.8 [71]
N-chloromethyl-brucine Small molecule or natural product Click here for species-specific activity table Hs Negative 4.6 pKd 71
pKd 4.6 [71]
N-chloromethyl-brucine Small molecule or natural product Click here for species-specific activity table Hs Positive 4.6 pKd 71
pKd 4.6 [71]
brucine Small molecule or natural product Click here for species-specific activity table Hs Positive 4.3 – 4.6