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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 3,10-11,104,159
Mouse 7 466 6 B1 Chrm2 cholinergic receptor, muscarinic 2, cardiac 82
Rat 7 466 4q22 Chrm2 cholinergic receptor, muscarinic 2 137
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:  47
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:  68
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:  68
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 74
pKd 8.8 [74]
[3H]oxotremorine-M Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Full agonist 8.7 pKd 6
pKd 8.7 [6]
NNC 11-1585 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 10.1 pKi 24
pKi 10.1 [24]
NNC 11-1607 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.2 pKi 24
pKi 8.2 [24]
pentylthio-TZTP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.9 pKi 61
pKi 7.9 [61]
methacholine Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Rn Agonist 7.2 pKi 102,109
pKi 7.2 (Ki 5.9x10-8 M) [102,109]
NNC 11-1314 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.2 pKi 24
pKi 7.2 [24]
xanomeline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.9 – 7.4 pKi 146,153
pKi 6.9 – 7.4 [146,153]
oxotremorine Small molecule or natural product Click here for species-specific activity table Rn Full agonist 6.5 pKi 67
pKi 6.5 [67]
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 67
pKi 6.4 [67]
cevimeline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.1 pKi 80
pKi 6.1 (Ki 8.54x10-7 M) [80]
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 61,109
pKi 5.0 – 6.6 [61,109]
arecaidine propargyl ester Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.7 pKi 61
pKi 5.7 [61]
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 67
pKi 5.7 [67]
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 23,61,65
pKi 4.3 – 6.5 [23,61,65]
McN-A-343 Small molecule or natural product Click here for species-specific activity table Rn Partial agonist 4.7 – 6.0 pKi 71
pKi 4.7 – 6.0 [71]
arecoline Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.2 pKi 61,100,109
pKi 5.2 [61,100,109]
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 23,61
pKi 4.2 – 5.7 [23,61]
methylfurmethide Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 pKi 61
pKi 4.9 [61]
oxotremorine-M Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 pKi 61
pKi 4.9 [61]
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 61,109
pKi 4.9 [61,109]
furtrethonium Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.5 pKi 61
pKi 4.5 [61]
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 61,109
pKi 4.0 [61,109]
iperoxo Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 9.8 pEC50 113-114
pEC50 9.8 [113-114]
(+)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.2 – 6.4 pEC50 35,46
pEC50 6.2 – 6.4 [35,46]
(-)-aceclidine Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 5.6 – 5.7 pEC50 35,46
pEC50 5.6 – 5.7 [35,46]
[18F]FP-TZTP Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Full agonist - - 59
[59]
View species-specific agonist tables
Agonist Comments
The binding data for McN-A-343 [71] is found on rat heart.
Please consult references [13,75,109,145,152] for further details of the activity of some of the ligands in this list.
Pilocarpine has been found to be a partial agonist [75,152] and a full agonist [145] 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 99
pA2 >6.3 [99]
[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 60,104
pKd 10.1 – 10.6 (Kd 7.94x10-11 – 2.51x10-11 M) [60,104]
[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 111
pKd 10.3 [111]
[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 20,52,60,62,66,73,145
pKd 9.3 – 9.9 (Kd 5.2x10-10 – 1.4x10-10 M) [20,52,60,62,66,73,145]
[3H]clidinium Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.6 pKd 67
pKd 9.6 [67]
[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 123
pKd 9.5 [123]
[3H]clidinium Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.5 pKd 67
pKd 9.5 [67]
[3H]4NMPB Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.4 pKd 123
pKd 9.4 [123]
[3H]AF DX-384 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 9.0 pKd 21,89,141
pKd 9.0 [21,89,141]
biperiden Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.2 pKd 9
pKd 8.2 (Kd 6.3x10-9 M) [9]
Cy3B-telenzepine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Hs Antagonist 10.4 pKi 95
pKi 10.4 [95]
tiotropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.9 – 10.7 pKi 31,106,130,132
pKi 9.9 – 10.7 [31,106,130,132]
umeclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.8 pKi 70,111
pKi 9.8 (Ki 1.5x10-10 M) [70,111]
tripitramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.6 pKi 81
pKi 9.6 [81]
ipratropium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.3 – 9.8 pKi 52,106
pKi 9.3 – 9.8 [52,106]
revefenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.5 pKi 51
pKi 9.5 (Ki 3.02x10-10 M) [51]
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 54
pKi 9.5 [54]
THRX160209 Small molecule or natural product Hs Antagonist 9.5 pKi 124
pKi 9.5 [124]
mepenzolic acid Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.2 pKi 154
pKi 9.2 (Ki 6.8x10-10 M) [154]
atropine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 9.0 – 9.1 pKi 64,67
pKi 9.0 – 9.1 [64,67]
dexetimide Small molecule or natural product Approved drug Primary target of this compound Hs Antagonist 8.9 pKi 67
pKi 8.9 [67]
dexetimide Small molecule or natural product Approved drug Rn Antagonist 8.8 pKi 67
pKi 8.8 [67]
Alexa-488-telenzepine Small molecule or natural product Click here for species-specific activity table Ligand is labelled Hs Antagonist 8.8 pKi 95
pKi 8.8 [95]
scopolamine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.7 pKi 9,54
pKi 8.7 [9,54]
SCH 57790 Small molecule or natural product Hs Antagonist 8.6 pKi 69
pKi 8.6 [69]
AE9C90CB Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.6 pKi 120
pKi 8.6 [120]
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 96
pKi 8.6 (Ki 2.6x10-9 M) [96]
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 28,52,54,104
pKi 7.8 – 9.2 [28,52,54,104]
tolterodine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inverse agonist 8.4 – 8.5 pKi 44,120
pKi 8.4 – 8.5 [44,120]
4-DAMP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 33
pKi 8.4 [33]
AQ-RA 741 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.4 pKi 33,44
pKi 8.4 [33,44]
4-DAMP Small molecule or natural product Click here for species-specific activity table Rn Antagonist 8.2 pKi 64,67
pKi 8.2 [64,67]
himbacine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.9 – 8.4 pKi 33,63,67,88
pKi 7.9 – 8.4 [33,63,67,88]
AFDX384 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.1 – 8.2 pKi 28,33
pKi 8.1 – 8.2 [28,33]
ethopropazine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 8.1 pKi 15
pKi 8.1 (Ki 7.2x10-9 M) [15]
Description: Displacement of [H]QNB binding in rat hindbrain brain homogenate.
oxybutynin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 – 8.1 pKi 30,120
pKi 7.9 – 8.1 [30,120]
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 122
pKi 7.9 (Ki 1.18x10-8 M) [122]
oxybutynin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inverse agonist 7.9 pKi 30
pKi 7.9 (Ki 1.175x10-8 M) [30]
himbacine Small molecule or natural product Rn Antagonist 7.9 pKi 67
pKi 7.9 [67]
methoctramine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 – 8.4 pKi 14,33,37,50,67,94
pKi 7.3 – 8.4 [14,33,37,50,67,94]
hexocyclium Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.6 pKi 14
pKi 7.6 [14]
(S)-dimetindene Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 7.5 pKi 18
pKi 7.5 (Ki 3.02x10-8 M) [18]
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 14
pKi 7.5 [14]
UH-AH 37 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.3 – 7.4 pKi 44,151
pKi 7.3 – 7.4 [44,151]
methoctramine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 7.3 pKi 67
pKi 7.3 [67]
darifenacin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inverse agonist 7.2 – 7.3 pKi 44,52,120
pKi 7.2 – 7.3 [44,52,120]
tropicamide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.2 pKi 28
pKi 7.2 [28]
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 55,120
pKi 6.9 – 7.1 [55,120]
dosulepin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.0 pKi 122
pKi 7.0 (Ki 1.09x10-7 M) [122]
otenzepad Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 – 7.2 pKi 14,67
pKi 6.7 – 7.2 [14,67]
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 67
pKi 6.9 [67]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Rn Antagonist 6.7 – 6.8 pKi 64,67
pKi 6.7 – 6.8 [64,67]
hexahydrosiladifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.6 – 6.8 pKi 14,37,67
pKi 6.6 – 6.8 [14,37,67]
hexahydrodifenidol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.7 pKi 14
pKi 6.7 [14]
dicyclomine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.6 pKi 14
pKi 6.6 [14]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Rn Antagonist 5.3 – 7.4 pKi 64,67,123
pKi 5.3 – 7.4 [64,67,123]
p-F-HHSiD Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.1 – 6.6 pKi 37,54
pKi 6.1 – 6.6 [37,54]
pirenzepine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.0 – 6.7 pKi 14,33,50,54,63,67,94,151
pKi 6.0 – 6.7 [14,33,50,54,63,67,94,151]
VU0255035 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 118
pKi 6.2 [118]
muscarinic toxin 3 Peptide Click here for species-specific activity table Hs Antagonist <6.0 pKi 63
pKi <6.0 [63]
otenzepad Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.6 – 7.3 pKi 64,67,123
pKi 4.6 – 7.3 [64,67,123]
lithocholylcholine Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.4 pKi 23
pKi 5.4 [23]
guanylpirenzepine Small molecule or natural product Click here for species-specific activity table Rn Antagonist 5.3 pKi 144
pKi 5.3 [144]
muscarinic toxin 7 Peptide Click here for species-specific activity table Hs Antagonist <5.0 pKi 97
pKi <5.0 [97]
levetimide Small molecule or natural product Hs Antagonist 5.0 pKi 67
pKi 5.0 [67]
levetimide Small molecule or natural product Rn Antagonist 4.8 pKi 67
pKi 4.8 [67]
ML381 Small molecule or natural product Click here for species-specific activity table Hs Antagonist <4.5 pKi 42
pKi <4.5 (Ki >3x10-5 M) [42]
aclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 10.1 pIC50 106,132
pIC50 10.1 [106,132]
glycopyrrolate Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.7 – 9.5 pIC50 127,130
pIC50 8.7 – 9.5 [127,130]
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 105
pIC50 6.2 (IC50 5.73x10-7 M) [105]
View species-specific antagonist tables
Antagonist Comments
Dexetimide is the optical isomer of levetimide [67].

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 [9].
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 136
pKd 8.5 [136]
C7/3-phth Small molecule or natural product Hs Negative 7.1 pKd 2,25
pKd 7.1 [2,25]
W-84 Small molecule or natural product Hs Negative 6.0 – 7.5 pKd 91,136
pKd 6.0 – 7.5 [91,136]
alcuronium Small molecule or natural product Click here for species-specific activity table Hs Negative 6.1 – 6.9 pKd 2,61,136
pKd 6.1 – 6.9 [2,61,136]
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 26,73
pKd 5.9 – 6.3 [26,73]
WIN 51,708 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.9 pKd 78
pKd 5.9 [78]
KT 5823 Small molecule or natural product Click here for species-specific activity table Hs Positive 5.7 pKd 77
pKd 5.7 [77]
LY2119620 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 5.5 – 5.7 pKd 29,68
pKd 5.5 – 5.7 [29,68]
WIN 62,577 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.3 pKd 78
pKd 5.3 [78]
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Positive 5.1 pKd 77
pKd 5.1 [77]
vincamine Small molecule or natural product Click here for species-specific activity table Hs Neutral 5.1 pKd 61
pKd 5.1 [61]
Gö 7874 Small molecule or natural product Click here for species-specific activity table Hs Negative 5.0 pKd 77
pKd 5.0 [77]
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 61,73,136
pKd 4.9 – 5.0 [61,73,136]
N-benzyl brucine Small molecule or natural product Click here for species-specific activity table Hs Negative 4.8 pKd 76
pKd 4.8 [76]
N-benzyl brucine Small molecule or natural product Click here for species-specific activity table Hs Positive 4.8 pKd 76
pKd 4.8 [76]
N-chloromethyl-brucine Small molecule or natural product Click here for species-specific activity table