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

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M1 receptor

Target not currently curated in GtoImmuPdb

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

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 11,99
Mouse 7 460 19 A Chrm1 cholinergic receptor, muscarinic 1, CNS 85,109
Rat 7 460 1q43-q51 Chrm1 cholinergic receptor, muscarinic 1 66,97,117,125
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:  124
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 24
pKi 9.9 [24]
NNC 11-1607 Hs Full agonist 8.6 pKi 24
pKi 8.6 [24]
pentylthio-TZTP Hs Full agonist 8.6 pKi 60
pKi 8.6 [60]
NNC 11-1314 Hs Full agonist 7.4 pKi 24
pKi 7.4 [24]
xanomeline Hs Partial agonist 6.7 – 7.9 pKi 25,61,132,144
pKi 6.7 – 7.9 [25,61,132,144]
sabcomeline Hs Partial agonist 6.7 pKi 144
pKi 6.7 [144]
arecaidine propargyl ester Hs Full agonist 6.4 pKi 60
pKi 6.4 [60]
LY593093 Hs Partial agonist 6.2 pKi 134
pKi 6.2 [134]
AC-42 Hs Full agonist 6.2 pKi 70
pKi 6.2 [70]
oxotremorine Rn Partial agonist 6.0 pKi 87
pKi 6.0 [87]
arecoline Hs Full agonist 5.7 pKi 60
pKi 5.7 [60]
oxotremorine-M Rn Full agonist 5.6 pKi 87
pKi 5.6 [87]
oxotremorine Hs Partial agonist 5.5 pKi 60
pKi 5.5 [60]
cevimeline Hs Agonist 5.3 pKi 79
pKi 5.3 (Ki 4.85x10-6 M) [79]
Description: Displacement of [3H]QNB from cloned receptor.
arecoline Rn Partial agonist 5.3 pKi 87
pKi 5.3 [87]
McN-A-343 Rn Partial agonist 5.1 pKi 87
pKi 5.1 [87]
oxotremorine-M Hs Full agonist 5.1 pKi 60
pKi 5.1 [60]
pilocarpine Hs Partial agonist 5.1 pKi 60
pKi 5.1 [60]
McN-A-343 Hs Partial agonist 4.8 – 5.2 pKi 104
pKi 4.8 – 5.2 [104]
acetylcholine Rn Full agonist 5.0 pKi 23
pKi 5.0 [23]
pilocarpine Rn Partial agonist 4.9 pKi 87
pKi 4.9 [87]
milameline Hs Partial agonist 4.8 pKi 144
pKi 4.8 [144]
acetylcholine Hs Full agonist 4.3 – 4.9 pKi 60,72
pKi 4.3 – 4.9 [60,72]
methylfurmethide Hs Full agonist 4.6 pKi 60
pKi 4.6 [60]
(-)-YM796 Hs Partial agonist 4.3 – 4.8 pKi 135
pKi 4.3 – 4.8 [135]
(±)YM796 Hs Partial agonist 4.1 – 4.7 pKi 135
pKi 4.1 – 4.7 [135]
carbachol Hs Full agonist 3.2 – 5.3 pKi 25,60,144
pKi 3.2 – 5.3 [25,60,144]
furtrethonium Hs Full agonist 4.1 pKi 60
pKi 4.1 [60]
bethanechol Hs Full agonist 4.0 pKi 60
pKi 4.0 [60]
carbachol Rn Full agonist 3.9 pKi 23
pKi 3.9 [23]
bethanechol Rn Full agonist 3.7 pKi 87
pKi 3.7 [87]
AZD6088 Hs Partial agonist 8.3 pEC50 91
pEC50 8.3 (EC50 5x10-9 M) [91]
methacholine Rn Agonist 6.4 pEC50 96
pEC50 6.4 (EC50 4x10-7 M) [96]
(+)-aceclidine Hs Full agonist 5.4 pEC50 32
pEC50 5.4 [32]
(-)-aceclidine Hs Partial agonist 5.0 pEC50 32
pEC50 5.0 [32]
[11C]butylthio-TZTP Hs Full agonist - - 35
[35]
[11C]xanomeline Hs Full agonist - - 35
[35]
SPP1 N/A Agonist - - 14
[14]
View species-specific agonist tables
Agonist Comments
Please consult references [16,74,104,130,141] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [74,104,141] as well as a full agonist [130] at the M1 receptor; oxotremorine has also been found to be a partial agonist [74,104,130] as well as a full agonist [104] 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 26,99
pKd 10.6 – 10.8 (Kd 2.51x10-11 – 1.58x10-11 M) [26,99]
Cy3B-telenzepine Hs Antagonist 10.5 pKd 53
pKd 10.5 [53]
[3H]N-methyl scopolamine Hs Antagonist 9.4 – 10.3 pKd 22,25-26,55,60-62,64,72
pKd 9.4 – 10.3 (Kd 4.2x10-10 – 5x10-11 M) [22,25-26,55,60-62,64,72]
[3H]N-methyl scopolamine Rn Antagonist 9.7 pKd 23,130
pKd 9.7 [23,130]
biperiden Hs Antagonist 9.3 pKd 10
pKd 9.3 (Kd 4.8x10-10 M) [10]
Alexa-488-telenzepine Hs Antagonist 9.3 pKd 53
pKd 9.3 [53]
[3H]darifenacin Hs Antagonist 8.8 pKd 113
pKd 8.8 [113]
[3H]pirenzepine Hs Antagonist 7.9 pKd 133
pKd 7.9 (Kd 1.4x10-8 M) [133]
[3H]pirenzepine Rn Antagonist 7.7 – 7.9 pKd 34,48
pKd 7.7 – 7.9 [34,48]
otenzepad Hs Antagonist 6.2 pKd 33
pKd 6.2 [33]
N-methyl scopolamine Hs Antagonist 9.9 pKi 37
pKi 9.9 [37]
umeclidinium Hs Antagonist 9.8 pKi 68,107
pKi 9.8 (Ki 1.6x10-10 M) [68,107]
propantheline Hs Antagonist 9.7 pKi 57
pKi 9.7 [57]
AE9C90CB Hs Antagonist 9.7 pKi 112
pKi 9.7 [112]
tiotropium Hs Antagonist 9.6 pKi 30
pKi 9.6 [30]
[3H](+)telenzepine Rn Antagonist 9.4 pKi 34
pKi 9.4 [34]
revefenacin Hs Antagonist 9.4 pKi 52
pKi 9.4 (Ki 4.17x10-10 M) [52]
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 17,23,63
pKi 9.0 – 9.7 [17,23,63]
ipratropium Hs Antagonist 9.3 pKi 55
pKi 9.3 [55]
4-DAMP Hs Antagonist 9.2 pKi 31
pKi 9.2 [31]
dicyclomine Hs Antagonist 9.1 pKi 5
pKi 9.1 (Ki 8.3x10-10 M) [5]
atropine Hs Antagonist 8.5 – 9.6 pKi 25,37,55,57,99,113
pKi 8.5 – 9.6 [25,37,55,57,99,113]
benzatropine Rn Antagonist 9.0 pKi 93
pKi 9.0 (Ki 9.5x10-10 M) [93]
Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine Hs Antagonist 9.0 pKi 57
pKi 9.0 [57]
4-DAMP Rn Antagonist 8.9 pKi 63
pKi 8.9 [63]
trihexyphenidyl Hs Antagonist 8.9 pKi 5
pKi 8.9 (Ki 1.35x10-9 M) [5]
tripitramine Hs Antagonist 8.8 pKi 82
pKi 8.8 [82]
silahexocyclium Rn Antagonist 8.7 pKi 17
pKi 8.7 [17]
UH-AH 37 Hs Antagonist 8.6 – 8.7 pKi 42,140
pKi 8.6 – 8.7 [42,140]
hexocyclium Rn Antagonist 8.6 pKi 17
pKi 8.6 [17]
oxybutynin Hs Antagonist 8.6 pKi 29,58,112
pKi 8.6 (Ki 2.4x10-9 M) [29,58,112]
tolterodine Hs Antagonist 8.5 – 8.7 pKi 42,112
pKi 8.5 – 8.7 [42,112]
ethopropazine Rn Antagonist 8.5 pKi 18
pKi 8.5 (Ki 3.1x10-9 M) [18]
Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
oxybutynin Rn Antagonist 8.2 pKi 92
pKi 8.2 [92]
pirenzepine Hs Antagonist 7.8 – 8.3 pKi 17,31,51,57,62,140
pKi 7.8 – 8.3 [17,31,51,57,62,140]
hexahydrodifenidol Rn Antagonist 8.0 pKi 17
pKi 8.0 [17]
solifenacin Rn Antagonist 8.0 pKi 92
pKi 8.0 [92]
darifenacin Hs Antagonist 7.5 – 8.3 pKi 42,51,55,58,112
pKi 7.5 – 8.3 [42,51,55,58,112]
pirenzepine Rn Antagonist 7.8 – 7.9 pKi 17,63
pKi 7.8 – 7.9 [17,63]
amitriptyline Hs Antagonist 7.8 pKi 116
pKi 7.8 (Ki 1.47x10-8 M) [116]
methoctramine Rn Antagonist 7.8 pKi 17
pKi 7.8 [17]
VU0255035 Hs Antagonist 7.8 pKi 110
pKi 7.8 (Ki 1.487x10-8 M) [110]
dosulepin Hs Antagonist 7.7 pKi 116
pKi 7.7 (Ki 1.8x10-8 M) [116]
hexahydrosiladifenidol Hs Antagonist 7.7 pKi 33
pKi 7.7 [33]
hexahydrosiladifenidol Rn Antagonist 7.4 – 7.9 pKi 17,63
pKi 7.4 – 7.9 [17,63]
solifenacin Hs Antagonist 7.6 pKi 58,112
pKi 7.6 [58,112]
AFDX384 Hs Antagonist 7.5 pKi 31
pKi 7.5 [31]
p-F-HHSiD Hs Antagonist 7.1 – 7.8 pKi 33,57
pKi 7.1 – 7.8 [33,57]
muscarinic toxin 1 Hs Antagonist 7.3 – 7.6 pKi 37,49
pKi 7.3 – 7.6 [37,49]
guanylpirenzepine Rn Antagonist 7.3 – 7.6 pKi 3,129
pKi 7.3 – 7.6 [3,129]
AQ-RA 741 Hs Antagonist 7.2 – 7.5 pKi 31,42
pKi 7.2 – 7.5 [31,42]
muscarinic toxin 3 Hs Antagonist 7.1 pKi 62
pKi 7.1 [62]
BODIPY-pirenzepine Hs Antagonist 7.0 pKi 59
pKi 7.0 [59]
methoctramine Hs Antagonist 6.6 – 7.3 pKi 31,33,51,113
pKi 6.6 – 7.3 [31,33,51,113]
himbacine Hs Antagonist 6.7 – 7.1 pKi 31,62,89
pKi 6.7 – 7.1 [31,62,89]
(S)-dimetindene Hs Antagonist 6.7 pKi 20
pKi 6.7 (Ki 1.906x10-7 M) [20]
Description: Binding to hM1 receptors expressed in CHO cells.
muscarinic toxin 2 Hs Antagonist 6.4 pKi 49
pKi 6.4 [49]
otenzepad Rn Antagonist 5.9 – 6.3 pKi 17,63
pKi 5.9 – 6.3 [17,63]
lithocholylcholine Rn Antagonist 5.6 pKi 23
pKi 5.6 [23]
ML381 Hs Antagonist <5.0 pKi 39
pKi <5.0 (Ki >1x10-5 M) [39]
glycopyrrolate Hs Antagonist 9.9 pIC50 118
pIC50 9.9 (IC50 1.26x10-10 M) [118]
Description: Assay uses glycopyrronium bromide
aclidinium Hs Antagonist 9.9 pIC50 102
pIC50 9.9 (IC50 1.4x10-10 M) [102]
Description: Human M1 receptors expressed in CHO-K1 cells
solifenacin Hs Antagonist 7.2 pIC50 101
pIC50 7.2 (IC50 6.35x10-8 M) [101]
[18F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate Rn Antagonist - - 65
[65]
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 [94]).

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 [18], 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 1-2,21,81
pKB 4.0 – 4.8 [1-2,21,81]
KT 5720 Hs Positive 6.4 pKd 76
pKd 6.4 (Kd 3.98x10-7 M) [76]
staurosporine Hs Positive 5.9 pKd 76
pKd 5.9 [76]
Gö 7874 Hs Negative 5.8 pKd 76
pKd 5.8 [76]
WIN 51,708 Hs Negative 5.8 pKd 77
pKd 5.8 [77]
KT 5823 Hs Positive 5.7 pKd 76
pKd 5.7 [76]
WIN 62,577 Hs Negative 5.5 pKd 77
pKd 5.5 [77]
brucine Hs Positive 4.5 – 5.8 pKd 60,75
pKd 4.5 – 5.8 (Kd 3x10-5 – 1.78x10-6 M) [60,75]
K-252a Hs Positive 5.1 pKd 76
pKd 5.1 [76]
vinburnine Hs Neutral 5.1 pKd 60
pKd 5.1 [60]
alcuronium Hs Negative 5.0 pKd 60
pKd 5.0 [60]
strychnine Hs Neutral 4.9 – 5.0 pKd 60,72
pKd 4.9 – 5.0 [60,72]
strychnine