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

Top ▲

M1 receptor

Target not currently curated in GtoImmuPdb

Target id: 13

Nomenclature: M1 receptor

Family: Acetylcholine receptors (muscarinic)

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 12,101
Mouse 7 460 19 A Chrm1 cholinergic receptor, muscarinic 1, CNS 87,111
Rat 7 460 1q43-q51 Chrm1 cholinergic receptor, muscarinic 1 67,99,119,127
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
Pharos
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:  126
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
NNC 11-1585 Hs Full agonist 9.9 pKi 25
pKi 9.9 [25]
NNC 11-1607 Hs Full agonist 8.6 pKi 25
pKi 8.6 [25]
pentylthio-TZTP Hs Full agonist 8.6 pKi 61
pKi 8.6 [61]
NNC 11-1314 Hs Full agonist 7.4 pKi 25
pKi 7.4 [25]
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 26,62,134,146
pKi 6.7 – 7.9 [26,62,134,146]
sabcomeline Hs Partial agonist 6.7 pKi 146
pKi 6.7 [146]
arecaidine propargyl ester Hs Full agonist 6.4 pKi 61
pKi 6.4 [61]
LY593093 Hs Partial agonist 6.2 pKi 136
pKi 6.2 [136]
AC-42 Hs Full agonist 6.2 pKi 71
pKi 6.2 [71]
oxotremorine Rn Partial agonist 6.0 pKi 89
pKi 6.0 [89]
arecoline Hs Full agonist 5.7 pKi 61
pKi 5.7 [61]
oxotremorine-M Rn Full agonist 5.6 pKi 89
pKi 5.6 [89]
oxotremorine Hs Partial agonist 5.5 pKi 61
pKi 5.5 [61]
cevimeline Hs Agonist 5.3 pKi 80
pKi 5.3 (Ki 4.85x10-6 M) [80]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Rn Partial agonist 5.3 pKi 89
pKi 5.3 [89]
McN-A-343 Rn Partial agonist 5.1 pKi 89
pKi 5.1 [89]
oxotremorine-M Hs Full agonist 5.1 pKi 61
pKi 5.1 [61]
pilocarpine Hs Partial agonist 5.1 pKi 61
pKi 5.1 [61]
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 106
pKi 4.8 – 5.2 [106]
acetylcholine Rn Full agonist 5.0 pKi 24
pKi 5.0 [24]
pilocarpine Rn Partial agonist 4.9 pKi 89
pKi 4.9 [89]
milameline Hs Partial agonist 4.8 pKi 146
pKi 4.8 [146]
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 61,73
pKi 4.3 – 4.9 [61,73]
methylfurmethide Hs Full agonist 4.6 pKi 61
pKi 4.6 [61]
(-)-YM796 Hs Partial agonist 4.3 – 4.8 pKi 137
pKi 4.3 – 4.8 [137]
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 137
pKi 4.1 – 4.7 [137]
carbachol Hs Full agonist 3.2 – 5.3 pKi 26,61,146
pKi 3.2 – 5.3 [26,61,146]
furtrethonium Hs Full agonist 4.1 pKi 61
pKi 4.1 [61]
bethanechol Hs Full agonist 4.0 pKi 61
pKi 4.0 [61]
carbachol Rn Full agonist 3.9 pKi 24
pKi 3.9 [24]
bethanechol Rn Full agonist 3.7 pKi 89
pKi 3.7 [89]
AZD6088 Hs Partial agonist 8.3 pEC50 93
pEC50 8.3 (EC50 5x10-9 M) [93]
methacholine Rn Agonist 6.4 pEC50 98
pEC50 6.4 (EC50 4x10-7 M) [98]
(+)-aceclidine Hs Full agonist 5.4 pEC50 33
pEC50 5.4 [33]
(-)-aceclidine Hs Partial agonist 5.0 pEC50 33
pEC50 5.0 [33]
[11C]butylthio-TZTP Hs Full agonist - - 36
[36]
[11C]xanomeline Hs Full agonist - - 36
[36]
SPP1 N/A Agonist - - 15
[15]
View species-specific agonist tables
Agonist Comments
Please consult references [17,75,106,132,143] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [75,106,143] as well as a full agonist [132] at the M1 receptor; oxotremorine has also been found to be a partial agonist [75,106,132] as well as a full agonist [106] at the M1 receptor.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]QNB Hs Antagonist 10.6 – 10.8 pKd 27,101
pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [27,101]
Cy3B-telenzepine Hs Antagonist 10.5 pKd 54
pKd 10.5 [54]
[3H]N-methyl scopolamine Hs Antagonist 9.4 – 10.3 pKd 23,26-27,56,61-63,65,73
pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [23,26-27,56,61-63,65,73]
[3H]N-methyl scopolamine Rn Antagonist 9.7 pKd 24,132
pKd 9.7 [24,132]
biperiden Hs Antagonist 9.3 pKd 11
pKd 9.3 (Kd 4.8x10-10 M) [11]
Alexa-488-telenzepine Hs Antagonist 9.3 pKd 54
pKd 9.3 [54]
[3H]darifenacin Hs Antagonist 8.8 pKd 115
pKd 8.8 [115]
[3H]pirenzepine Hs Antagonist 7.9 pKd 135
pKd 7.9 (Kd 1.4x10-8 M) [135]
[3H]pirenzepine Rn Antagonist 7.7 – 7.9 pKd 35,49
pKd 7.7 – 7.9 [35,49]
otenzepad Hs Antagonist 6.2 pKd 34
pKd 6.2 [34]
N-methyl scopolamine Hs Antagonist 9.9 pKi 38
pKi 9.9 [38]
umeclidinium Hs Antagonist 9.8 pKi 69,109
pKi 9.8 (Ki 1.6x10-10 M) [69,109]
propantheline Hs Antagonist 9.7 pKi 58
pKi 9.7 [58]
AE9C90CB Hs Antagonist 9.7 pKi 114
pKi 9.7 [114]
tiotropium Hs Antagonist 9.6 pKi 31
pKi 9.6 [31]
[3H](+)telenzepine Rn Antagonist 9.4 pKi 35
pKi 9.4 [35]
revefenacin Hs Antagonist 9.4 pKi 53
pKi 9.4 (Ki 4.17x10-10 M) [53]
Description: Determined from a radioligand binding assay using membranes from CHO‐K1 cells expressing the hM1 receptor, and displacement of [3H]NMS tracer.
atropine Rn Antagonist 9.0 – 9.7 pKi 18,24,64
pKi 9.0 – 9.7 [18,24,64]
ipratropium Hs Antagonist 9.3 pKi 56
pKi 9.3 [56]
4-DAMP Hs Antagonist 9.2 pKi 32
pKi 9.2 [32]
dicyclomine Hs Antagonist 9.1 pKi 5
pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Hs Antagonist 8.5 – 9.6 pKi 26,38,56,58,101,115
pKi 8.5 – 9.6 [26,38,56,58,101,115]
benzatropine Rn Antagonist 9.0 pKi 95
pKi 9.0 (Ki 9.5x10-10 M) [95]
Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine Hs Antagonist 9.0 pKi 58
pKi 9.0 [58]
4-DAMP Rn Antagonist 8.9 pKi 64
pKi 8.9 [64]
trihexyphenidyl Hs Antagonist 8.9 pKi 5
pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Hs Antagonist 8.8 pKi 83
pKi 8.8 [83]
silahexocyclium Rn Antagonist 8.7 pKi 18
pKi 8.7 [18]
UH-AH 37 Hs Antagonist 8.6 – 8.7 pKi 43,142
pKi 8.6 – 8.7 [43,142]
hexocyclium Rn Antagonist 8.6 pKi 18
pKi 8.6 [18]
oxybutynin Hs Antagonist 8.6 pKi 30,59,114
pKi 8.6 (Ki 2.4x10-9 M) [30,59,114]
tolterodine Hs Antagonist 8.5 – 8.7 pKi 43,114
pKi 8.5 – 8.7 [43,114]
ethopropazine Rn Antagonist 8.5 pKi 19
pKi 8.5 (Ki 3.1x10-9 M) [19]
Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
oxybutynin Rn Antagonist 8.2 pKi 94
pKi 8.2 [94]
pirenzepine Hs Antagonist 7.8 – 8.3 pKi 18,32,52,58,63,142
pKi 7.8 – 8.3 [18,32,52,58,63,142]
hexahydrodifenidol Rn Antagonist 8.0 pKi 18
pKi 8.0 [18]
solifenacin Rn Antagonist 8.0 pKi 94
pKi 8.0 [94]
darifenacin Hs Antagonist 7.5 – 8.3 pKi 43,52,56,59,114
pKi 7.5 – 8.3 [43,52,56,59,114]
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 18,64
pKi 7.8 – 7.9 [18,64]
amitriptyline Hs Antagonist 7.8 pKi 118
pKi 7.8 (Ki 1.47x10-8 M) [118]
methoctramine Rn Antagonist 7.8 pKi 18
pKi 7.8 [18]
VU0255035 Hs Antagonist 7.8 pKi 112
pKi 7.8 (Ki 1.487x10-8 M) [112]
dosulepin Hs Antagonist 7.7 pKi 118
pKi 7.7 (Ki 1.8x10-8 M) [118]
hexahydrosiladifenidol Hs Antagonist 7.7 pKi 34
pKi 7.7 [34]
hexahydrosiladifenidol Rn Antagonist 7.4 – 7.9 pKi 18,64
pKi 7.4 – 7.9 [18,64]
solifenacin Hs Antagonist 7.6 pKi 59,114
pKi 7.6 [59,114]
AFDX384 Hs Antagonist 7.5 pKi 32
pKi 7.5 [32]
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 34,58
pKi 7.1 – 7.8 [34,58]
muscarinic toxin 1 Hs Antagonist 7.3 – 7.6 pKi 38,50
pKi 7.3 – 7.6 [38,50]
guanylpirenzepine Rn Antagonist 7.3 – 7.6 pKi 3,131
pKi 7.3 – 7.6 [3,131]
AQ-RA 741 Hs Antagonist 7.2 – 7.5 pKi 32,43
pKi 7.2 – 7.5 [32,43]
muscarinic toxin 3 Hs Antagonist 7.1 pKi 63
pKi 7.1 [63]
BODIPY-pirenzepine Hs Antagonist 7.0 pKi 60
pKi 7.0 [60]
methoctramine Hs Antagonist 6.6 – 7.3 pKi 32,34,52,115
pKi 6.6 – 7.3 [32,34,52,115]
himbacine Hs Antagonist 6.7 – 7.1 pKi 32,63,91
pKi 6.7 – 7.1 [32,63,91]
(S)-dimetindene Hs Antagonist 6.7 pKi 21
pKi 6.7 (Ki 1.906x10-7 M) [21]
Description: Binding to hM1 receptors expressed in CHO cells.
muscarinic toxin 2 Hs Antagonist 6.4 pKi 50
pKi 6.4 [50]
otenzepad Rn Antagonist 5.9 – 6.3 pKi 18,64
pKi 5.9 – 6.3 [18,64]
lithocholylcholine Rn Antagonist 5.6 pKi 24
pKi 5.6 [24]
ML381 Hs Antagonist <5.0 pKi 40
pKi <5.0 (Ki >1x10-5 M) [40]
glycopyrrolate Hs Antagonist 9.9 pIC50 120
pIC50 9.9 (IC50 1.26x10-10 M) [120]
Description: Assay uses glycopyrronium bromide
aclidinium Hs Antagonist 9.9 pIC50 104
pIC50 9.9 (IC50 1.4x10-10 M) [104]
Description: Human M1 receptors expressed in CHO-K1 cells
solifenacin Hs Antagonist 7.2 pIC50 103
pIC50 7.2 (IC50 6.35x10-8 M) [103]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Rn Antagonist - - 66
[66]
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 [96]).

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 [11]. Ethopropazine appears to have highest affinity for the M1 subtype in rat brain homegenates [19], 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 Value Parameter Reference
benzoquinazolinone 12 Hs Positive 6.6 pKB 1
pKB 6.6 [1]
BQCA Hs Positive 4.0 – 4.8 pKB 1-2,22,82
pKB 4.0 – 4.8 [1-2,22,82]
KT 5720 Hs Positive 6.4 pKd 77
pKd 6.4 (Kd 3.98x10-7 M) [77]
staurosporine Hs Positive 5.9 pKd 77
pKd 5.9 [77]
Gö 7874 Hs Negative 5.8 pKd 77
pKd 5.8 [77]
WIN 51,708 Hs Negative 5.8 pKd 78
pKd 5.8 [78]
KT 5823 Hs Positive 5.7 pKd 77
pKd 5.7 [77]
WIN 62,577 Hs Negative 5.5 pKd 78
pKd 5.5 [78]
brucine Hs Positive 4.5 – 5.8 pKd 61,76
pKd 4.5 – 5.8 (Kd 3x10-5 – 1.78x10-6 M) [61,76]
K-252a Hs Positive 5.1 pKd 77
pKd 5.1 [77]
vinburnine Hs Neutral 5.1 pKd 61
pKd 5.1 [61]
alcuronium Hs Negative 5.0 pKd 61
pKd 5.0 [61]
strychnine Hs Neutral 4.9 – 5.0 pKd 61,73
pKd 4.9 – 5.0 [61,73]
strychnine