M<sub>1</sub> receptor | Acetylcholine receptors (muscarinic) | IUPHAR/BPS Guide to PHARMACOLOGY

M1 receptor

Target id: 13

Nomenclature: M1 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

   GtoImmuPdb view: OFF :     Currently no data for M1 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 460 11q13 CHRM1 cholinergic receptor muscarinic 1 11,96
Mouse 7 460 19 A Chrm1 cholinergic receptor, muscarinic 1, CNS 82,106
Rat 7 460 1q43-q51 Chrm1 cholinergic receptor, muscarinic 1 63,94,114,122
Previous and Unofficial Names
M1 muscarinic acetylcholine receptor | Chrm-1 | M1R | cholinergic receptor, muscarinic 1 | cholinergic receptor | cholinergic receptor, muscarinic 1, CNS
Database Links
Specialist databases
GPCRDB acm1_human (Hs), acm1_mouse (Mm), acm1_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:  Crystal structure of the human M1 muscarinic acetylcholine receptor bound to antagonist tiotropium.
PDB Id:  5CXV
Ligand:  tiotropium
Resolution:  2.7Å
Species:  Human
References:  121
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 Affinity Units Reference
NNC 11-1585 Hs Full agonist 9.9 pKi 22
pKi 9.9 [22]
NNC 11-1607 Hs Full agonist 8.6 pKi 22
pKi 8.6 [22]
pentylthio-TZTP Hs Full agonist 8.6 pKi 57
pKi 8.6 [57]
NNC 11-1314 Hs Full agonist 7.4 pKi 22
pKi 7.4 [22]
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 23,58,129,141
pKi 6.7 – 7.9 [23,58,129,141]
sabcomeline Hs Partial agonist 6.7 pKi 141
pKi 6.7 [141]
arecaidine propargyl ester Hs Full agonist 6.4 pKi 57
pKi 6.4 [57]
LY593093 Hs Partial agonist 6.2 pKi 131
pKi 6.2 [131]
AC-42 Hs Full agonist 6.2 pKi 67
pKi 6.2 [67]
oxotremorine Rn Partial agonist 6.0 pKi 84
pKi 6.0 [84]
arecoline Hs Full agonist 5.7 pKi 57
pKi 5.7 [57]
oxotremorine-M Rn Full agonist 5.6 pKi 84
pKi 5.6 [84]
oxotremorine Hs Partial agonist 5.5 pKi 57
pKi 5.5 [57]
cevimeline Hs Agonist 5.3 pKi 76
pKi 5.3 (Ki 4.85x10-6 M) [76]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Rn Partial agonist 5.3 pKi 84
pKi 5.3 [84]
McN-A-343 Rn Partial agonist 5.1 pKi 84
pKi 5.1 [84]
oxotremorine-M Hs Full agonist 5.1 pKi 57
pKi 5.1 [57]
pilocarpine Hs Partial agonist 5.1 pKi 57
pKi 5.1 [57]
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 101
pKi 4.8 – 5.2 [101]
acetylcholine Rn Full agonist 5.0 pKi 21
pKi 5.0 [21]
pilocarpine Rn Partial agonist 4.9 pKi 84
pKi 4.9 [84]
milameline Hs Partial agonist 4.8 pKi 141
pKi 4.8 [141]
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 57,69
pKi 4.3 – 4.9 [57,69]
methylfurmethide Hs Full agonist 4.6 pKi 57
pKi 4.6 [57]
(-)-YM796 Hs Partial agonist 4.3 – 4.8 pKi 132
pKi 4.3 – 4.8 [132]
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 132
pKi 4.1 – 4.7 [132]
carbachol Hs Full agonist 3.2 – 5.3 pKi 23,57,141
pKi 3.2 – 5.3 [23,57,141]
furtrethonium Hs Full agonist 4.1 pKi 57
pKi 4.1 [57]
bethanechol Hs Full agonist 4.0 pKi 57
pKi 4.0 [57]
carbachol Rn Full agonist 3.9 pKi 21
pKi 3.9 [21]
bethanechol Rn Full agonist 3.7 pKi 84
pKi 3.7 [84]
AZD6088 Hs Partial agonist 8.3 pEC50 88
pEC50 8.3 (EC50 5x10-9 M) [88]
methacholine Rn Agonist 6.4 pEC50 93
pEC50 6.4 (EC50 4x10-7 M) [93]
(+)-aceclidine Hs Full agonist 5.4 pEC50 30
pEC50 5.4 [30]
(-)-aceclidine Hs Partial agonist 5.0 pEC50 30
pEC50 5.0 [30]
[11C]butylthio-TZTP Hs Full agonist - - 33
[33]
[11C]xanomeline Hs Full agonist - - 33
[33]
View species-specific agonist tables
Agonist Comments
Please consult references [15,71,101,127,138] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [71,101,138] as well as a full agonist [127] at the M1 receptor; oxotremorine has also been found to be a partial agonist [71,101,127] as well as a full agonist [101] at the M1 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[3H]QNB Hs Antagonist 10.6 – 10.8 pKd 24,96
pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [24,96]
Cy3B-telenzepine Hs Antagonist 10.5 pKd 50
pKd 10.5 [50]
[3H]N-methyl scopolamine Hs Antagonist 9.4 – 10.3 pKd 20,23-24,52,57-59,61,69
pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [20,23-24,52,57-59,61,69]
[3H]N-methyl scopolamine Rn Antagonist 9.7 pKd 21,127
pKd 9.7 [21,127]
biperiden Hs Antagonist 9.3 pKd 10
pKd 9.3 (Kd 4.8x10-10 M) [10]
Alexa-488-telenzepine Hs Antagonist 9.3 pKd 50
pKd 9.3 [50]
[3H]darifenacin Hs Antagonist 8.8 pKd 110
pKd 8.8 [110]
[3H]pirenzepine Hs Antagonist 7.9 pKd 130
pKd 7.9 (Kd 1.4x10-8 M) [130]
[3H]pirenzepine Rn Antagonist 7.7 – 7.9 pKd 32,46
pKd 7.7 – 7.9 [32,46]
otenzepad Hs Antagonist 6.2 pKd 31
pKd 6.2 [31]
N-methyl scopolamine Hs Antagonist 9.9 pKi 35
pKi 9.9 [35]
umeclidinium Hs Antagonist 9.8 pKi 65,104
pKi 9.8 (Ki 1.6x10-10 M) [65,104]
propantheline Hs Antagonist 9.7 pKi 54
pKi 9.7 [54]
AE9C90CB Hs Antagonist 9.7 pKi 109
pKi 9.7 [109]
tiotropium Hs Antagonist 9.6 pKi 28
pKi 9.6 [28]
[3H](+)telenzepine Rn Antagonist 9.4 pKi 32
pKi 9.4 [32]
atropine Rn Antagonist 9.0 – 9.7 pKi 16,21,60
pKi 9.0 – 9.7 [16,21,60]
ipratropium Hs Antagonist 9.3 pKi 52
pKi 9.3 [52]
4-DAMP Hs Antagonist 9.2 pKi 29
pKi 9.2 [29]
dicyclomine Hs Antagonist 9.1 pKi 5
pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Hs Antagonist 8.5 – 9.6 pKi 23,35,52,54,96,110
pKi 8.5 – 9.6 [23,35,52,54,96,110]
benzatropine Rn Antagonist 9.0 pKi 90
pKi 9.0 (Ki 9.5x10-10 M) [90]
Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine Hs Antagonist 9.0 pKi 54
pKi 9.0 [54]
4-DAMP Rn Antagonist 8.9 pKi 60
pKi 8.9 [60]
trihexyphenidyl Hs Antagonist 8.9 pKi 5
pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Hs Antagonist 8.8 pKi 79
pKi 8.8 [79]
silahexocyclium Rn Antagonist 8.7 pKi 16
pKi 8.7 [16]
UH-AH 37 Hs Antagonist 8.6 – 8.7 pKi 40,137
pKi 8.6 – 8.7 [40,137]
hexocyclium Rn Antagonist 8.6 pKi 16
pKi 8.6 [16]
oxybutynin Hs Antagonist 8.6 pKi 27,55,109
pKi 8.6 (Ki 2.4x10-9 M) [27,55,109]
tolterodine Hs Antagonist 8.5 – 8.7 pKi 40,109
pKi 8.5 – 8.7 [40,109]
ethopropazine Rn Antagonist 8.5 pKi 17
pKi 8.5 (Ki 3.1x10-9 M) [17]
Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
oxybutynin Rn Antagonist 8.2 pKi 89
pKi 8.2 [89]
pirenzepine Hs Antagonist 7.8 – 8.3 pKi 16,29,49,54,59,137
pKi 7.8 – 8.3 [16,29,49,54,59,137]
hexahydrodifenidol Rn Antagonist 8.0 pKi 16
pKi 8.0 [16]
solifenacin Rn Antagonist 8.0 pKi 89
pKi 8.0 [89]
darifenacin Hs Antagonist 7.5 – 8.3 pKi 40,49,52,55,109
pKi 7.5 – 8.3 [40,49,52,55,109]
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 16,60
pKi 7.8 – 7.9 [16,60]
amitriptyline Hs Antagonist 7.8 pKi 113
pKi 7.8 (Ki 1.47x10-8 M) [113]
methoctramine Rn Antagonist 7.8 pKi 16
pKi 7.8 [16]
VU0255035 Hs Antagonist 7.8 pKi 107
pKi 7.8 (Ki 1.487x10-8 M) [107]
dosulepin Hs Antagonist 7.7 pKi 113
pKi 7.7 (Ki 1.8x10-8 M) [113]
hexahydrosiladifenidol Hs Antagonist 7.7 pKi 31
pKi 7.7 [31]
hexahydrosiladifenidol Rn Antagonist 7.4 – 7.9 pKi 16,60
pKi 7.4 – 7.9 [16,60]
solifenacin Hs Antagonist 7.6 pKi 55,109
pKi 7.6 [55,109]
AFDX384 Hs Antagonist 7.5 pKi 29
pKi 7.5 [29]
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 31,54
pKi 7.1 – 7.8 [31,54]
muscarinic toxin 1 Hs Antagonist 7.3 – 7.6 pKi 35,47
pKi 7.3 – 7.6 [35,47]
guanylpirenzepine Rn Antagonist 7.3 – 7.6 pKi 3,126
pKi 7.3 – 7.6 [3,126]
AQ-RA 741 Hs Antagonist 7.2 – 7.5 pKi 29,40
pKi 7.2 – 7.5 [29,40]
muscarinic toxin 3 Hs Antagonist 7.1 pKi 59
pKi 7.1 [59]
BODIPY-pirenzepine Hs Antagonist 7.0 pKi 56
pKi 7.0 [56]
methoctramine Hs Antagonist 6.6 – 7.3 pKi 29,31,49,110
pKi 6.6 – 7.3 [29,31,49,110]
himbacine Hs Antagonist 6.7 – 7.1 pKi 29,59,86
pKi 6.7 – 7.1 [29,59,86]
muscarinic toxin 2 Hs Antagonist 6.4 pKi 47
pKi 6.4 [47]
otenzepad Rn Antagonist 5.9 – 6.3 pKi 16,60
pKi 5.9 – 6.3 [16,60]
lithocholylcholine Rn Antagonist 5.6 pKi 21
pKi 5.6 [21]
ML381 Hs Antagonist <5.0 pKi 37
pKi <5.0 (Ki >1x10-5 M) [37]
glycopyrrolate Hs Antagonist 9.9 pIC50 115
pIC50 9.9 (IC50 1.26x10-10 M) [115]
Description: Assay uses glycopyrronium bromide
aclidinium Hs Antagonist 9.9 pIC50 99
pIC50 9.9 (IC50 1.4x10-10 M) [99]
Description: Human M1 receptors expressed in CHO-K1 cells
solifenacin Hs Antagonist 7.2 pIC50 98
pIC50 7.2 (IC50 6.35x10-8 M) [98]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Rn Antagonist - - 62
[62]
View species-specific antagonist tables
Antagonist Comments
Recombinant MT7 (rMT7) is often used for bioassays due to the limited availability of the M1 muscarinic receptor-selective mamba toxin MT7 or m1-toxin 1 (rMT7 has comparable affinity for M1 [91]).

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 [10]. Ethopropazine appears to have highest affinity for the M1 subtype in rat brain homegenates [17], so the M1 receptor is the likely primary human target of this drug.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
benzoquinazolinone 12 Hs Positive 6.6 pKB 1
pKB 6.6 [1]
BQCA Hs Positive 4.0 – 4.8 pKB 1-2,19,78
pKB 4.0 – 4.8 [1-2,19,78]
KT 5720 Hs Positive 6.4 pKd 73
pKd 6.4 (Kd 3.98x10-7 M) [73]
staurosporine Hs Positive 5.9 pKd 73
pKd 5.9 [73]
Gö 7874 Hs Negative 5.8 pKd 73
pKd 5.8 [73]
WIN 51,708 Hs Negative 5.8 pKd 74
pKd 5.8 [74]
KT 5823 Hs Positive 5.7 pKd 73
pKd 5.7 [73]
WIN 62,577 Hs Negative 5.5 pKd 74
pKd 5.5 [74]
brucine Hs Positive 4.5 – 5.8 pKd 57,72
pKd 4.5 – 5.8 (Kd 3x10-5 – 1.78x10-6 M) [57,72]
K-252a Hs Positive 5.1 pKd 73
pKd 5.1 [73]
vinburnine Hs Neutral 5.1 pKd 57
pKd 5.1 [57]
alcuronium Hs Negative 5.0 pKd 57
pKd 5.0 [57]
strychnine Hs Neutral 4.9 – 5.0 pKd 57,69
pKd 4.9 – 5.0 [57,69]
strychnine Hs Negative 4.9 pKd 69
pKd 4.9 [69]
vincamine Hs Neutral 4.8 pKd 57
pKd 4.8 [57]
brucine Hs Neutral 4.5 pKd 72
pKd 4.5 [72]
N-benzyl brucine Hs Negative 4.4 pKd 72
pKd 4.4 [72]
N-chloromethyl-brucine Hs Negative 4.1 pKd 72
pKd 4.1 [72]
thiochrome Hs Neutral 4.1 pKd 70
pKd 4.1 [70]
brucine N-oxide Hs Neutral 3.2 pKd 72
pKd 3.2 [72]
brucine N-oxide Hs Positive 3.2 pKd