M<sub>1</sub> receptor | Acetylcholine receptors (muscarinic)

M₁ receptor

Target not currently curated in GtoImmuPdb

Target id: 13

Nomenclature: M₁ receptor

Family: Acetylcholine receptors (muscarinic)

Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Natural/Endogenous Ligands
Agonists
Antagonists
Allosteric Modulators
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
General Comments
References
Contributors
How to cite this page

Gene and Protein Information
class A G protein-coupled receptor
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	7	460	11q12.3	CHRM1	cholinergic receptor muscarinic 1	12,107
Mouse	7	460	19 A	Chrm1	cholinergic receptor, muscarinic 1, CNS	91,119
Rat	7	460	1q43	Chrm1	cholinergic receptor, muscarinic 1	71,105,127,137

Previous and Unofficial Names
M1 muscarinic acetylcholine receptor \| Chrm-1 \| M1R \| cholinergic receptor, muscarinic 1 \| cholinergic receptor \| cholinergic receptor, muscarinic 1, CNS

Previous and Unofficial Names

Database Links
Specialist databases
GPCRDB	acm1_human (Hs), acm1_mouse (Mm), acm1_rat (Rn)
Other databases
ChEMBL Target	CHEMBL216 (Hs), CHEMBL3733 (Mm), CHEMBL276 (Rn)
DrugBank Target	P11229 (Hs)
Ensembl Gene	ENSG00000168539 (Hs), ENSMUSG00000032773 (Mm), ENSRNOG00000018385 (Rn)
Entrez Gene	1128 (Hs), 12669 (Mm), 25229 (Rn)
Human Protein Atlas	ENSG00000168539 (Hs)
KEGG Gene	hsa:1128 (Hs), mmu:12669 (Mm), rno:25229 (Rn)
OMIM	118510 (Hs)
Pharos	P11229 (Hs)
RefSeq Nucleotide	NM_000738 (Hs), NM_007698 (Mm), NM_080773 (Rn)
RefSeq Protein	NP_000729 (Hs), NP_031724 (Mm), NP_542951 (Rn)
SynPHARM	82388 (in complex with tiotropium)
UniProtKB	P11229 (Hs), P12657 (Mm), P08482 (Rn)
Wikipedia	CHRM1 (Hs)

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:	136

Natural/Endogenous Ligands
acetylcholine

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Agonists

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Ligand		Sp.	Action	Value	Parameter	Reference
NNC 11-1585		Hs	Full agonist	9.9	pK_i	26
⤷	pK_i 9.9 [26]
NNC 11-1607		Hs	Full agonist	8.6	pK_i	26
⤷	pK_i 8.6 [26]
pentylthio-TZTP		Hs	Full agonist	8.6	pK_i	64
⤷	pK_i 8.6 [64]
NNC 11-1314		Hs	Full agonist	7.4	pK_i	26
⤷	pK_i 7.4 [26]
xanomeline		Hs	Partial agonist	6.7 – 7.9	pK_i	27,145,157
⤷	pK_i 6.7 – 7.9 [27,145,157]
sabcomeline		Hs	Partial agonist	6.7	pK_i	157
⤷	pK_i 6.7 [157]
arecaidine propargyl ester		Hs	Full agonist	6.4	pK_i	64
⤷	pK_i 6.4 [64]
LY593093		Hs	Partial agonist	6.2	pK_i	147
⤷	pK_i 6.2 [147]
AC-42		Hs	Full agonist	6.2	pK_i	75
⤷	pK_i 6.2 [75]
oxotremorine		Rn	Partial agonist	6.0	pK_i	93
⤷	pK_i 6.0 [93]
arecoline		Hs	Full agonist	5.7	pK_i	64,103,112
⤷	pK_i 5.7 [64,103,112]
oxotremorine-M		Rn	Full agonist	5.6	pK_i	93
⤷	pK_i 5.6 [93]
oxotremorine		Hs	Partial agonist	5.5	pK_i	64,112
⤷	pK_i 5.5 [64,112]
cevimeline		Hs	Agonist	5.3	pK_i	84
⤷	pK_i 5.3 (K_i 4.85x10^-6 M) [84] Description: Displacement of [³H]QNB from cloned receptor.
arecoline		Rn	Partial agonist	5.3	pK_i	93
⤷	pK_i 5.3 [93]
McN-A-343		Rn	Partial agonist	5.1	pK_i	93
⤷	pK_i 5.1 [93]
oxotremorine-M		Hs	Full agonist	5.1	pK_i	64
⤷	pK_i 5.1 [64]
pilocarpine		Hs	Partial agonist	5.1	pK_i	64,112
⤷	pK_i 5.1 [64,112]
McN-A-343		Hs	Partial agonist	4.8 – 5.2	pK_i	112
⤷	pK_i 4.8 – 5.2 [112]
acetylcholine		Rn	Full agonist	5.0	pK_i	25
⤷	pK_i 5.0 [25]
pilocarpine		Rn	Partial agonist	4.9	pK_i	93
⤷	pK_i 4.9 [93]
milameline		Hs	Partial agonist	4.8	pK_i	157
⤷	pK_i 4.8 [157]
acetylcholine		Hs	Full agonist	4.3 – 4.9	pK_i	64,68
⤷	pK_i 4.3 – 4.9 [64,68]
methylfurmethide		Hs	Full agonist	4.6	pK_i	64
⤷	pK_i 4.6 [64]
(-)-YM796		Hs	Partial agonist	4.3 – 4.8	pK_i	148
⤷	pK_i 4.3 – 4.8 [148]
(±)YM796		Hs	Partial agonist	4.1 – 4.7	pK_i	148
⤷	pK_i 4.1 – 4.7 [148]
carbachol		Hs	Full agonist	3.2 – 5.3	pK_i	27,64,157
⤷	pK_i 3.2 – 5.3 [27,64,157]
furtrethonium		Hs	Full agonist	4.1	pK_i	64
⤷	pK_i 4.1 [64]
bethanechol		Hs	Full agonist	4.0	pK_i	64,112
⤷	pK_i 4.0 [64,112]
carbachol		Rn	Full agonist	3.9	pK_i	25
⤷	pK_i 3.9 [25]
bethanechol		Rn	Full agonist	3.7	pK_i	93
⤷	pK_i 3.7 [93]
AZD6088		Hs	Partial agonist	8.3	pEC₅₀	97
⤷	pEC₅₀ 8.3 (EC₅₀ 5x10^-9 M) [97]
methacholine		Rn	Agonist	6.4	pEC₅₀	104,112
⤷	pEC₅₀ 6.4 (EC₅₀ 4x10^-7 M) [104,112]
(+)-aceclidine		Hs	Full agonist	5.4	pEC₅₀	35
⤷	pEC₅₀ 5.4 [35]
(-)-aceclidine		Hs	Partial agonist	5.0	pEC₅₀	35
⤷	pEC₅₀ 5.0 [35]
[¹¹C]butylthio-TZTP		Hs	Full agonist	-	-	38
⤷	[38]
[¹¹C]xanomeline		Hs	Full agonist	-	-	38
⤷	[38]
iperoxo		Hs	Agonist	-	-	117
⤷	[117]
SPP1		N/A	Agonist	-	-	15
⤷	[15]

View species-specific agonist tables

Agonist Comments

Please consult references [17,79,112,143,154] for further details of the activity of some of the ligands in this list.

Pilocarpine has been found to be a partial agonist [79,112,154] as well as a full agonist [143] at the M₁ receptor; oxotremorine has also been found to be a partial agonist [79,112,143] as well as a full agonist [112] at the M₁ receptor.

Antagonists

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Ligand		Sp.	Action	Value	Parameter	Reference
[³H]QNB		Hs	Antagonist	10.6 – 10.8	pK_d	63,107
⤷	pK_d 10.6 – 10.8 (K_d 2.51x10^-11 – 1.58x10^-11 M) [63,107]
Cy3B-telenzepine		Hs	Antagonist	10.5	pK_d	56
⤷	pK_d 10.5 [56]
[³H]N-methyl scopolamine		Hs	Antagonist	9.4 – 10.3	pK_d	23,27-28,58,64-66,69,77
⤷	pK_d 9.4 – 10.3 (K_d 4.2x10^-10 – 5x10^-11 M) [23,27-28,58,64-66,69,77]
[³H]N-methyl scopolamine		Rn	Antagonist	9.7	pK_d	25,143
⤷	pK_d 9.7 [25,143]
biperiden		Hs	Antagonist	9.3	pK_d	11
⤷	pK_d 9.3 (K_d 4.8x10^-10 M) [11]
Alexa-488-telenzepine		Hs	Antagonist	9.3	pK_d	56
⤷	pK_d 9.3 [56]
[³H]darifenacin		Hs	Antagonist	8.8	pK_d	123
⤷	pK_d 8.8 [123]
[³H]pirenzepine		Hs	Antagonist	7.9	pK_d	24,116,139,146
⤷	pK_d 7.9 (K_d 1.4x10^-8 M) [24,116,139,146]
[³H]pirenzepine		Rn	Antagonist	7.7 – 7.9	pK_d	37,51
⤷	pK_d 7.7 – 7.9 [37,51]
otenzepad		Hs	Antagonist	6.2	pK_d	36
⤷	pK_d 6.2 [36]
tiotropium		Hs	Antagonist	9.6 – 10.7	pK_i	33,110,132,134
⤷	pK_i 9.6 – 10.7 [33,110,132,134]
N-methyl scopolamine		Hs	Antagonist	9.9	pK_i	40
⤷	pK_i 9.9 [40]
umeclidinium		Hs	Antagonist	9.8	pK_i	73,115
⤷	pK_i 9.8 (K_i 1.6x10^-10 M) [73,115]
propantheline		Hs	Antagonist	9.7	pK_i	60
⤷	pK_i 9.7 [60]
ipratropium		Hs	Antagonist	9.3 – 9.8	pK_i	58,110
⤷	pK_i 9.3 – 9.8 [58,110]
[³H](+)telenzepine		Rn	Antagonist	9.4	pK_i	37
⤷	pK_i 9.4 [37]
revefenacin		Hs	Antagonist	9.4	pK_i	55
⤷	pK_i 9.4 (K_i 4.17x10^-10 M) [55] 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	pK_i	18,25,67
⤷	pK_i 9.0 – 9.7 [18,25,67]
4-DAMP		Hs	Antagonist	9.3	pK_i	34
⤷	pK_i 9.3 [34]
dicyclomine		Hs	Antagonist	9.1	pK_i	5
⤷	pK_i 9.1 (K_i 8.3x10^-10 M) [5]
atropine		Hs	Antagonist	8.5 – 9.6	pK_i	27,40,58,60,107,123
⤷	pK_i 8.5 – 9.6 [27,40,58,60,107,123]
benzatropine		Rn	Antagonist	9.0	pK_i	99
⤷	pK_i 9.0 (K_i 9.5x10^-10 M) [99] Description: Displacement binding experiment using homogenised rat caudate putamen.
darifenacin		Hs	Antagonist	8.9 – 9.1	pK_i	45,58,122
⤷	pK_i 8.9 – 9.1 [45,58,122]
scopolamine		Hs	Antagonist	9.0	pK_i	30,60
⤷	pK_i 9.0 [30,60]
4-DAMP		Rn	Antagonist	8.9	pK_i	67
⤷	pK_i 8.9 [67]
trihexyphenidyl		Hs	Antagonist	8.9	pK_i	5
⤷	pK_i 8.9 (K_i 1.35x10^-9 M) [5]
tripitramine		Hs	Antagonist	8.8	pK_i	87
⤷	pK_i 8.8 [87]
silahexocyclium		Rn	Antagonist	8.7	pK_i	18
⤷	pK_i 8.7 [18]
hexocyclium		Rn	Antagonist	8.6	pK_i	18
⤷	pK_i 8.6 [18]
oxybutynin		Hs	Antagonist	8.6	pK_i	32,122
⤷	pK_i 8.6 (K_i 2.4x10^-9 M) [32,122]
ethopropazine		Rn	Antagonist	8.5	pK_i	19
⤷	pK_i 8.5 (K_i 3.1x10^-9 M) [19] Description: Displacement of [H]QNB binding in rat forebrain brain homogenate.
tolterodine		Hs	Antagonist	8.4 – 8.5	pK_i	45,122
⤷	pK_i 8.4 – 8.5 [45,122]
oxybutynin		Rn	Antagonist	8.2	pK_i	98
⤷	pK_i 8.2 [98]
hexahydrodifenidol		Rn	Antagonist	8.0	pK_i	18
⤷	pK_i 8.0 [18]
solifenacin		Rn	Antagonist	8.0	pK_i	98
⤷	pK_i 8.0 [98]
pirenzepine		Hs	Antagonist	7.6 – 8.3	pK_i	18,34,54,60,66,153
⤷	pK_i 7.6 – 8.3 [18,34,54,60,66,153]
pirenzepine		Rn	Antagonist	7.8 – 7.9	pK_i	18,67
⤷	pK_i 7.8 – 7.9 [18,67]
amitriptyline		Hs	Antagonist	7.8	pK_i	126
⤷	pK_i 7.8 (K_i 1.47x10^-8 M) [126]
methoctramine		Rn	Antagonist	7.8	pK_i	18
⤷	pK_i 7.8 [18]
VU0255035		Hs	Antagonist	7.8	pK_i	120
⤷	pK_i 7.8 (K_i 1.487x10^-8 M) [120]
dosulepin		Hs	Antagonist	7.7	pK_i	126
⤷	pK_i 7.7 (K_i 1.8x10^-8 M) [126]
hexahydrosiladifenidol		Hs	Antagonist	7.7	pK_i	36
⤷	pK_i 7.7 [36]
hexahydrosiladifenidol		Rn	Antagonist	7.4 – 7.9	pK_i	18,67
⤷	pK_i 7.4 – 7.9 [18,67]
solifenacin		Hs	Antagonist	7.6	pK_i	61,122
⤷	pK_i 7.6 [61,122]
AFDX384		Hs	Antagonist	7.5	pK_i	34
⤷	pK_i 7.5 [34]
p-F-HHSiD		Hs	Antagonist	7.1 – 7.8	pK_i	36,60
⤷	pK_i 7.1 – 7.8 [36,60]
muscarinic toxin 1		Hs	Antagonist	7.3 – 7.6	pK_i	40,52
⤷	pK_i 7.3 – 7.6 [40,52]
guanylpirenzepine		Rn	Antagonist	7.3 – 7.6	pK_i	3,142
⤷	pK_i 7.3 – 7.6 [3,142]
AQ-RA 741		Hs	Antagonist	7.2 – 7.5	pK_i	34,45
⤷	pK_i 7.2 – 7.5 [34,45]
muscarinic toxin 3		Hs	Antagonist	7.1	pK_i	66
⤷	pK_i 7.1 [66]
droxidopa		Hs	Antagonist	7.1	pK_i	30
⤷	pK_i 7.1 [30]
BODIPY-pirenzepine		Hs	Antagonist	7.0	pK_i	62
⤷	pK_i 7.0 [62]
methoctramine		Hs	Antagonist	6.6 – 7.3	pK_i	34,36,54,123
⤷	pK_i 6.6 – 7.3 [34,36,54,123]
himbacine		Hs	Antagonist	6.7 – 7.1	pK_i	34,66,95
⤷	pK_i 6.7 – 7.1 [34,66,95]
(S)-dimetindene		Hs	Antagonist	6.7	pK_i	21
⤷	pK_i 6.7 (K_i 1.906x10^-7 M) [21] Description: Binding to hM1 receptors expressed in CHO cells.
muscarinic toxin 2		Hs	Antagonist	6.4	pK_i	52
⤷	pK_i 6.4 [52]
otenzepad		Rn	Antagonist	5.9 – 6.3	pK_i	18,67
⤷	pK_i 5.9 – 6.3 [18,67]
lithocholylcholine		Rn	Antagonist	5.6	pK_i	25
⤷	pK_i 5.6 [25]
ML381		Hs	Antagonist	<5.0	pK_i	42
⤷	pK_i <5.0 (K_i >1x10^-5 M) [42]
aclidinium		Hs	Antagonist	10.1 – 10.2	pIC₅₀	110,134
⤷	pIC₅₀ 10.1 – 10.2 [110,134]
glycopyrrolate		Hs	Antagonist	9.6 – 10.1	pIC₅₀	128,132
⤷	pIC₅₀ 9.6 – 10.1 [128,132] Description: Assay uses glycopyrronium bromide
solifenacin		Hs	Antagonist	7.2	pIC₅₀	109
⤷	pIC₅₀ 7.2 (IC₅₀ 6.35x10^-8 M) [109]
[¹⁸F](R,R)-quinuclidinyl-4-fluoromethyl-benzilate		Rn	Antagonist	-	-	70
⤷	[70]

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 [100]).

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

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Ligand		Sp.	Action	Value	Parameter	Reference
benzoquinazolinone 12		Hs	Positive	6.6	pK_B	1
⤷	pK_B 6.6 [1]
BQCA		Hs	Positive	4.0 – 4.8	pK_B	1-2,22,86
⤷	pK_B 4.0 – 4.8 [1-2,22,86]
KT 5720		Hs	Positive	6.4	pK_d	81
⤷	pK_d 6.4 (K_d 3.98x10^-7 M) [81]
staurosporine		Hs	Positive	5.9	pK_d	81
⤷	pK_d 5.9 [81]
Gö 7874		Hs	Negative	5.8	pK_d	81
⤷	pK_d 5.8 [81]
WIN 51,708		Hs	Negative	5.8	pK_d	82
⤷	pK_d 5.8 [82]
KT 5823		Hs	Positive	5.7	pK_d	81
⤷	pK_d 5.7 [81]
WIN 62,577		Hs	Negative	5.5	pK_d	82
⤷	pK_d 5.5 [82]
brucine		Hs	Positive	4.5 – 5.8	pK_d	10,64,80
⤷	pK_d 4.5 – 5.8 (K_d 3x10^-5 – 1.78x10^-6 M) [10,64,80]
K-252a		Hs	Positive	5.1	pK_d	81
⤷	pK_d 5.1 [81]
vinburnine		Hs	Neutral	5.1	pK_d	64
⤷	pK_d 5.1 [64]
alcuronium		Hs	Negative	5.0	pK_d	64
⤷	pK_d 5.0 [64]
strychnine		Hs	Neutral	4.9 – 5.0	pK_d	64,77
⤷	pK_d 4.9 – 5.0 [64,77]
strychnine

M1 receptor

Contents:

M₁ receptor