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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)

Contents:

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 3,10-11,104,160
Mouse 7 466 6 B1 Chrm2 cholinergic receptor, muscarinic 2, cardiac 82
Rat 7 466 4q22 Chrm2 cholinergic receptor, muscarinic 2 138
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
Alphafold P08172 (Hs), Q9ERZ4 (Mm), P10980 (Rn)
ChEMBL Target CHEMBL211 (Hs), CHEMBL3197 (Mm), CHEMBL309 (Rn)
DrugBank Target P08172 (Hs)
Ensembl Gene ENSG00000181072 (Hs), ENSMUSG00000045613 (Mm), ENSRNOG00000046972 (Rn)
Entrez Gene 1129 (Hs), 243764 (Mm), 81645 (Rn)
Human Protein Atlas ENSG00000181072 (Hs)
KEGG Gene hsa:1129 (Hs), mmu:243764 (Mm), rno:81645 (Rn)
OMIM 118493 (Hs)
Pharos P08172 (Hs)
RefSeq Nucleotide NM_000739 (Hs), NM_203491 (Mm), NM_031016 (Rn)
RefSeq Protein NP_000730 (Hs), NP_987076 (Mm), NP_112278 (Rn)
SynPHARM 1190 (in complex with [3H]QNB)
UniProtKB P08172 (Hs), Q9ERZ4 (Mm), P10980 (Rn)
Wikipedia CHRM2 (Hs)
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]iperoxo Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Agonist 10.1 pKd 114
⤷ pKd 10.1 (Kd 8x10-11 M) [114]
[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 102,110
⤷ pKi 7.2 (Ki 5.9x10-8 M) [102,110]
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 Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 6.9 – 7.4 pKi 105,147,154
⤷ pKi 6.9 – 7.4 [105,147,154]
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 61,110
⤷ pKi 5.0 – 6.6 [61,110]
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 61,100,110
⤷ pKi 5.2 [61,100,110]
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 61,110
⤷ pKi 4.9 [61,110]
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 61,110
⤷ pKi 4.0 [61,110]
iperoxo Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 9.8 pEC50 114-115
⤷ pEC50 9.8 [114-115]
(+)-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 [13,75,110,146,153] for further details of the activity of some of the ligands in this list.
Pilocarpine has been found to be a partial agonist [75,153] and a full agonist [146] 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 112
⤷ pKd 10.3 [112]
[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 20,52,60,62,66,73,146
⤷ pKd 9.3 – 9.9 (Kd 5.2x10-10 – 1.4x10-10 M) [20,52,60,62,66,73,146]
[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 124
⤷ pKd 9.5 [124]
[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 124
⤷ pKd 9.4 [124]
[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 21,89,142
⤷ pKd 9.0 [21,89,142]
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 31,107,131,133
⤷ pKi 9.9 – 10.7 [31,107,131,133]
umeclidinium Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 9.8 pKi 70,112
⤷ pKi 9.8 (Ki 1.5x10-10 M) [70,112]
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 52,107
⤷ pKi 9.3 – 9.8 [52,107]
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 125
⤷ pKi 9.5 [125]
mepenzolic acid Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.2 pKi 155
⤷ pKi 9.2 (Ki 6.8x10-10 M) [155]
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 Ligand has a PDB structure 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 121
⤷ pKi 8.6 [121]
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 44,121
⤷ pKi 8.4 – 8.5 [44,121]
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 30,121
⤷ pKi 7.9 – 8.1 [30,121]
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 123
⤷ pKi 7.9 (Ki 1.18x10-8 M) [123]
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 44,152
⤷ pKi 7.3 – 7.4 [44,152]
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 44,52,121
⤷ pKi 7.2 – 7.3 [44,52,121]
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 55,121
⤷ pKi 6.9 – 7.1 [55,121]
dosulepin Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.0 pKi 123
⤷ pKi 7.0 (Ki 1.09x10-7 M) [123]
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 64,67,124
⤷ pKi 5.3 – 7.4 [64,67,124]
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 14,33,50,54,63,67,94,152
⤷ pKi 6.0 – 6.7 [14,33,50,54,63,67,94,152]
VU0255035 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 119
⤷ pKi 6.2 [119]
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 64,67,124
⤷ pKi 4.6 – 7.3 [64,67,124]
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 145
⤷ pKi 5.3 [145]
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 107,133
⤷ pIC50 10.1 [107,133]
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 128,131
⤷ pIC50 8.7 – 9.5 [128,131]
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 106
⤷ pIC50 6.2 (IC50 5.73x10-7 M) [106]
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 137
⤷ pKd 8.5 [137]
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 91,137
⤷ pKd 6.0 – 7.5 [91,137]
alcuronium Small molecule or natural product Click here for species-specific activity table Hs Negative 6.1 – 6.9 pKd 2,61,137
⤷ pKd 6.1 – 6.9 [2,61,137]
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]