M<sub>2</sub> receptor | Acetylcholine receptors (muscarinic) | IUPHAR/BPS Guide to PHARMACOLOGY

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M2 receptor

Target not currently curated in GtoImmuPdb

Target id: 14

Nomenclature: M2 receptor

Family: Acetylcholine receptors (muscarinic)

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 7 466 7q31-q35 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
M2 muscarinic acetylcholine receptor | AChR M2 | Chrm-2 | cholinergic receptor, muscarinic 2 | cholinergic receptor | cholinergic receptor, muscarinic 2, cardiac
Database Links
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
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
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
acetylcholine

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]acetylcholine Hs Agonist 8.8 pKd 69
pKd 8.8 [69]
[3H]oxotremorine-M Hs Full agonist 8.7 pKd 5
pKd 8.7 [5]
NNC 11-1585 Hs Full agonist 10.1 pKi 22
pKi 10.1 [22]
NNC 11-1607 Hs Full agonist 8.2 pKi 22
pKi 8.2 [22]
pentylthio-TZTP Hs Full agonist 7.9 pKi 57
pKi 7.9 [57]
methacholine Rn Agonist 7.2 pKi 95
pKi 7.2 (Ki 5.9x10-8 M) [95]
NNC 11-1314 Hs Full agonist 7.2 pKi 22
pKi 7.2 [22]
xanomeline Hs Full agonist 6.9 – 7.4 pKi 135,142
pKi 6.9 – 7.4 [135,142]
oxotremorine Rn Full agonist 6.5 pKi 62
pKi 6.5 [62]
acetylcholine Rn Full agonist 6.4 pKi 62
pKi 6.4 [62]
cevimeline Hs Agonist 6.1 pKi 75
pKi 6.1 (Ki 8.54x10-7 M) [75]
Description: Displacement of [3H]QNB from cloned receptor.
oxotremorine Hs Full agonist 5.0 – 6.6 pKi 57,62
pKi 5.0 – 6.6 [57,62]
arecaidine propargyl ester Hs Full agonist 5.7 pKi 57
pKi 5.7 [57]
carbachol Rn Full agonist 5.7 pKi 62
pKi 5.7 [62]
acetylcholine Hs Full agonist 4.3 – 6.5 pKi 21,57,62,68
pKi 4.3 – 6.5 [21,57,62,68]
McN-A-343 Rn Partial agonist 4.7 – 6.0 pKi 66
pKi 4.7 – 6.0 [66]
arecoline Hs Full agonist 5.2 pKi 57
pKi 5.2 [57]
carbachol Hs Full agonist 4.2 – 5.7 pKi 21,57,62
pKi 4.2 – 5.7 [21,57,62]
methylfurmethide Hs Full agonist 4.9 pKi 57
pKi 4.9 [57]
oxotremorine-M Hs Full agonist 4.9 pKi 57
pKi 4.9 [57]
pilocarpine Hs Partial agonist 4.9 pKi 57
pKi 4.9 [57]
furtrethonium Hs Full agonist 4.5 pKi 57
pKi 4.5 [57]
bethanechol Hs Full agonist 4.0 pKi 57
pKi 4.0 [57]
iperoxo Hs Full agonist 9.8 pEC50 106
pEC50 9.8 [106]
(+)-aceclidine Hs Full agonist 6.2 – 6.4 pEC50 32,43
pEC50 6.2 – 6.4 [32,43]
(-)-aceclidine Hs Partial agonist 5.6 – 5.7 pEC50 32,43
pEC50 5.6 – 5.7 [32,43]
[18F]FP-TZTP 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 Hs Antagonist >6.3 pA2 93
pA2 >6.3 [93]
[3H]QNB Hs Antagonist 10.1 – 10.6 pKd 97
pKd 10.1 – 10.6 (Kd 7.94x10-11 – 2.51x10-11 M) [97]
[3H]tiotropium Hs Antagonist 10.3 pKd 104
pKd 10.3 [104]
[3H]N-methyl scopolamine 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 Hs Antagonist 9.6 pKd 62
pKd 9.6 [62]
[3H]N-methyl scopolamine Rn Antagonist 9.5 pKd 115
pKd 9.5 [115]
[3H]clidinium Rn Antagonist 9.5 pKd 62
pKd 9.5 [62]
[3H]4NMPB Rn Antagonist 9.4 pKd 115
pKd 9.4 [115]
[3H]AF DX-384 Hs Antagonist 8.7 pKd 84
pKd 8.7 [84]
biperiden Hs Antagonist 8.2 pKd 8
pKd 8.2 (Kd 6.3x10-9 M) [8]
Cy3B-telenzepine Hs Antagonist 10.4 pKi 89
pKi 10.4 [89]
tiotropium Hs Antagonist 9.9 pKi 28
pKi 9.9 [28]
umeclidinium Hs Antagonist 9.8 pKi 65,104
pKi 9.8 (Ki 1.5x10-10 M) [65,104]
tripitramine Hs Antagonist 9.6 pKi 76
pKi 9.6 [76]
revefenacin 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 Hs Antagonist 9.5 pKi 51
pKi 9.5 [51]
THRX160209 Hs Antagonist 9.5 pKi 116
pKi 9.5 [116]
mepenzolic acid Hs Antagonist 9.2 pKi 143
pKi 9.2 (Ki 6.8x10-10 M) [143]
atropine Rn Antagonist 9.0 – 9.1 pKi 60,62
pKi 9.0 – 9.1 [60,62]
dexetimide Hs Antagonist 8.9 pKi 62
pKi 8.9 [62]
ipratropium Hs Antagonist 8.8 pKi 49
pKi 8.8 [49]
dexetimide Rn Antagonist 8.8 pKi 62
pKi 8.8 [62]
Alexa-488-telenzepine Hs Antagonist 8.8 pKi 89
pKi 8.8 [89]
scopolamine Hs Antagonist 8.7 pKi 51
pKi 8.7 [51]
SCH 57790 Hs Antagonist 8.6 pKi 64
pKi 8.6 [64]
AE9C90CB Hs Antagonist 8.6 pKi 112
pKi 8.6 [112]
benzatropine 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 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 Hs Inverse agonist 8.4 – 8.6 pKi 41,88,112
pKi 8.4 – 8.6 [41,88,112]
AQ-RA 741 Hs Antagonist 8.4 pKi 30,41
pKi 8.4 [30,41]
4-DAMP Hs Antagonist 8.3 pKi 62
pKi 8.3 [62]
4-DAMP Rn Antagonist 8.2 pKi 60,62
pKi 8.2 [60,62]
AFDX384 Hs Antagonist 8.2 pKi 30
pKi 8.2 [30]
himbacine Hs Antagonist 7.9 – 8.4 pKi 30,59,62,83
pKi 7.9 – 8.4 [30,59,62,83]
ethopropazine 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 Hs Antagonist 7.9 pKi 114
pKi 7.9 (Ki 1.18x10-8 M) [114]
oxybutynin Hs Inverse agonist 7.9 pKi 27
pKi 7.9 (Ki 1.175x10-8 M) [27]
himbacine Rn Antagonist 7.9 pKi 62
pKi 7.9 [62]
oxybutynin Hs Antagonist 7.7 – 8.1 pKi 52,112
pKi 7.7 – 8.1 [52,112]
methoctramine 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 Hs Antagonist 7.6 pKi 13
pKi 7.6 [13]
(S)-dimetindene 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 Hs Antagonist 7.5 pKi 13
pKi 7.5 [13]
UH-AH 37 Hs Antagonist 7.3 – 7.4 pKi 41,140
pKi 7.3 – 7.4 [41,140]
darifenacin 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 Rn Antagonist 7.3 pKi 62
pKi 7.3 [62]
solifenacin Hs Antagonist 6.9 – 7.1 pKi 52,112
pKi 6.9 – 7.1 [52,112]
dosulepin Hs Antagonist 7.0 pKi 114
pKi 7.0 (Ki 1.09x10-7 M) [114]
otenzepad Hs Antagonist 6.7 – 7.2 pKi 13,62
pKi 6.7 – 7.2 [13,62]
imipramine Hs Antagonist 6.9 pKi 62
pKi 6.9 [62]
hexahydrosiladifenidol Rn Antagonist 6.7 – 6.8 pKi 60,62
pKi 6.7 – 6.8 [60,62]
hexahydrosiladifenidol Hs Antagonist 6.6 – 6.8 pKi 13,34,62
pKi 6.6 – 6.8 [13,34,62]
hexahydrodifenidol Hs Antagonist 6.7 pKi 13
pKi 6.7 [13]
dicyclomine Hs Antagonist 6.6 pKi 13
pKi 6.6 [13]
pirenzepine Rn Antagonist 5.3 – 7.4 pKi 60,62,115
pKi 5.3 – 7.4 [60,62,115]
p-F-HHSiD Hs Antagonist 6.1 – 6.6 pKi 34,51
pKi 6.1 – 6.6 [34,51]
pirenzepine 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 Hs Antagonist 6.2 pKi 110
pKi 6.2 [110]
muscarinic toxin 3 Hs Antagonist <6.0 pKi 59
pKi <6.0 [59]
otenzepad Rn Antagonist 4.6 – 7.3 pKi 60,62,115
pKi 4.6 – 7.3 [60,62,115]
lithocholylcholine Hs Antagonist 5.4 pKi 21
pKi 5.4 [21]
guanylpirenzepine Rn Antagonist 5.3 pKi 133
pKi 5.3 [133]
muscarinic toxin 7 Hs Antagonist <5.0 pKi 91
pKi <5.0 [91]
levetimide Hs Antagonist 5.0 pKi 62
pKi 5.0 [62]
levetimide Rn Antagonist 4.8 pKi 62
pKi 4.8 [62]
ML381 Hs Antagonist <4.5 pKi 39
pKi <4.5 (Ki >3x10-5 M) [39]
aclidinium Hs Antagonist 9.8 pIC50 99
pIC50 9.8 (IC50 1.7x10-10 M) [99]
glycopyrrolate Hs Antagonist 9.3 pIC50 119
pIC50 9.3 (IC50 5.01x10-10 M) [119]
Description: Assay uses glycopyrronium bromide
solifenacin 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 Hs Positive 8.5 pKd 126
pKd 8.5 [126]
C7/3-phth Hs Negative 7.1 pKd 23
pKd 7.1 [23]
W-84 Hs Negative 6.0 – 7.5 pKd 86,126
pKd 6.0 – 7.5 [86,126]
alcuronium Hs Negative 6.1 – 6.9 pKd 57,126
pKd 6.1 – 6.9 [57,126]
gallamine Hs Negative 5.9 – 6.3 pKd 24,68
pKd 5.9 – 6.3 [24,68]
WIN 51,708 Hs Negative 5.9 pKd 73
pKd 5.9 [73]
KT 5823 Hs Positive 5.7 pKd 72
pKd 5.7 [72]
LY2119620 Hs Positive 5.7 pKd 26,63
pKd 5.7 [26,63]
WIN 62,577 Hs Negative 5.3 pKd 73
pKd 5.3 [73]
staurosporine Hs Positive 5.1 pKd 72
pKd 5.1 [72]
vincamine Hs Neutral 5.1 pKd 57
pKd 5.1 [57]
Gö 7874 Hs Negative 5.0 pKd 72
pKd 5.0 [72]
strychnine Hs Positive 4.9 – 5.0 pKd 57,68,126
pKd 4.9 – 5.0 [57,68,126]
N-benzyl brucine Hs Negative 4.8 pKd 71
pKd 4.8 [71]
N-benzyl brucine Hs Positive 4.8 pKd 71
pKd 4.8 [71]
N-chloromethyl-brucine Hs Negative 4.6 pKd 71
pKd 4.6 [71]
N-chloromethyl-brucine Hs Positive 4.6 pKd 71
pKd 4.6 [71]
brucine