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	12,101
Mouse	7	460	19 A	Chrm1	cholinergic receptor, muscarinic 1, CNS	87,111
Rat	7	460	1q43	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

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:	126

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	25
⤷	pK_i 9.9 [25]
NNC 11-1607		Hs	Full agonist	8.6	pK_i	25
⤷	pK_i 8.6 [25]
pentylthio-TZTP		Hs	Full agonist	8.6	pK_i	61
⤷	pK_i 8.6 [61]
NNC 11-1314		Hs	Full agonist	7.4	pK_i	25
⤷	pK_i 7.4 [25]
xanomeline		Hs	Partial agonist	6.7 – 7.9	pK_i	26,62,134,146
⤷	pK_i 6.7 – 7.9 [26,62,134,146]
sabcomeline		Hs	Partial agonist	6.7	pK_i	146
⤷	pK_i 6.7 [146]
arecaidine propargyl ester		Hs	Full agonist	6.4	pK_i	61
⤷	pK_i 6.4 [61]
LY593093		Hs	Partial agonist	6.2	pK_i	136
⤷	pK_i 6.2 [136]
AC-42		Hs	Full agonist	6.2	pK_i	71
⤷	pK_i 6.2 [71]
oxotremorine		Rn	Partial agonist	6.0	pK_i	89
⤷	pK_i 6.0 [89]
arecoline		Hs	Full agonist	5.7	pK_i	61
⤷	pK_i 5.7 [61]
oxotremorine-M		Rn	Full agonist	5.6	pK_i	89
⤷	pK_i 5.6 [89]
oxotremorine		Hs	Partial agonist	5.5	pK_i	61
⤷	pK_i 5.5 [61]
cevimeline		Hs	Agonist	5.3	pK_i	80
⤷	pK_i 5.3 (K_i 4.85x10^-6 M) [80] Description: Displacement of [³H]QNB from cloned receptor.
arecoline		Rn	Partial agonist	5.3	pK_i	89
⤷	pK_i 5.3 [89]
McN-A-343		Rn	Partial agonist	5.1	pK_i	89
⤷	pK_i 5.1 [89]
oxotremorine-M		Hs	Full agonist	5.1	pK_i	61
⤷	pK_i 5.1 [61]
pilocarpine		Hs	Partial agonist	5.1	pK_i	61
⤷	pK_i 5.1 [61]
McN-A-343		Hs	Partial agonist	4.8 – 5.2	pK_i	106
⤷	pK_i 4.8 – 5.2 [106]
acetylcholine		Rn	Full agonist	5.0	pK_i	24
⤷	pK_i 5.0 [24]
pilocarpine		Rn	Partial agonist	4.9	pK_i	89
⤷	pK_i 4.9 [89]
milameline		Hs	Partial agonist	4.8	pK_i	146
⤷	pK_i 4.8 [146]
acetylcholine		Hs	Full agonist	4.3 – 4.9	pK_i	61,73
⤷	pK_i 4.3 – 4.9 [61,73]
methylfurmethide		Hs	Full agonist	4.6	pK_i	61
⤷	pK_i 4.6 [61]
(-)-YM796		Hs	Partial agonist	4.3 – 4.8	pK_i	137
⤷	pK_i 4.3 – 4.8 [137]
(±)YM796		Hs	Partial agonist	4.1 – 4.7	pK_i	137
⤷	pK_i 4.1 – 4.7 [137]
carbachol		Hs	Full agonist	3.2 – 5.3	pK_i	26,61,146
⤷	pK_i 3.2 – 5.3 [26,61,146]
furtrethonium		Hs	Full agonist	4.1	pK_i	61
⤷	pK_i 4.1 [61]
bethanechol		Hs	Full agonist	4.0	pK_i	61
⤷	pK_i 4.0 [61]
carbachol		Rn	Full agonist	3.9	pK_i	24
⤷	pK_i 3.9 [24]
bethanechol		Rn	Full agonist	3.7	pK_i	89
⤷	pK_i 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

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Ligand		Sp.	Action	Value	Parameter	Reference
[³H]QNB		Hs	Antagonist	10.6 – 10.8	pK_d	27,101
⤷	pK_d 10.6 – 10.8 (K_d 2.51x10^-11 – 1.58x10^-11 M) [27,101]
Cy3B-telenzepine		Hs	Antagonist	10.5	pK_d	54
⤷	pK_d 10.5 [54]
[³H]N-methyl scopolamine		Hs	Antagonist	9.4 – 10.3	pK_d	23,26-27,56,61-63,65,73
⤷	pK_d 9.4 – 10.3 (K_d 4.2x10^-10 – 5x10^-11 M) [23,26-27,56,61-63,65,73]
[³H]N-methyl scopolamine		Rn	Antagonist	9.7	pK_d	24,132
⤷	pK_d 9.7 [24,132]
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	54
⤷	pK_d 9.3 [54]
[³H]darifenacin		Hs	Antagonist	8.8	pK_d	115
⤷	pK_d 8.8 [115]
[³H]pirenzepine		Hs	Antagonist	7.9	pK_d	135
⤷	pK_d 7.9 (K_d 1.4x10^-8 M) [135]
[³H]pirenzepine		Rn	Antagonist	7.7 – 7.9	pK_d	35,49
⤷	pK_d 7.7 – 7.9 [35,49]
otenzepad		Hs	Antagonist	6.2	pK_d	34
⤷	pK_d 6.2 [34]
N-methyl scopolamine		Hs	Antagonist	9.9	pK_i	38
⤷	pK_i 9.9 [38]
umeclidinium		Hs	Antagonist	9.8	pK_i	69,109
⤷	pK_i 9.8 (K_i 1.6x10^-10 M) [69,109]
propantheline		Hs	Antagonist	9.7	pK_i	58
⤷	pK_i 9.7 [58]
AE9C90CB		Hs	Antagonist	9.7	pK_i	114
⤷	pK_i 9.7 [114]
tiotropium		Hs	Antagonist	9.6	pK_i	31
⤷	pK_i 9.6 [31]
[³H](+)telenzepine		Rn	Antagonist	9.4	pK_i	35
⤷	pK_i 9.4 [35]
revefenacin		Hs	Antagonist	9.4	pK_i	53
⤷	pK_i 9.4 (K_i 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	pK_i	18,24,64
⤷	pK_i 9.0 – 9.7 [18,24,64]
ipratropium		Hs	Antagonist	9.3	pK_i	56
⤷	pK_i 9.3 [56]
4-DAMP		Hs	Antagonist	9.2	pK_i	32
⤷	pK_i 9.2 [32]
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	26,38,56,58,101,115
⤷	pK_i 8.5 – 9.6 [26,38,56,58,101,115]
benzatropine		Rn	Antagonist	9.0	pK_i	95
⤷	pK_i 9.0 (K_i 9.5x10^-10 M) [95] Description: Displacement binding experiment using homogenised rat caudate putamen.
scopolamine		Hs	Antagonist	9.0	pK_i	58
⤷	pK_i 9.0 [58]
4-DAMP		Rn	Antagonist	8.9	pK_i	64
⤷	pK_i 8.9 [64]
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	83
⤷	pK_i 8.8 [83]
silahexocyclium		Rn	Antagonist	8.7	pK_i	18
⤷	pK_i 8.7 [18]
UH-AH 37		Hs	Antagonist	8.6 – 8.7	pK_i	43,142
⤷	pK_i 8.6 – 8.7 [43,142]
hexocyclium		Rn	Antagonist	8.6	pK_i	18
⤷	pK_i 8.6 [18]
oxybutynin		Hs	Antagonist	8.6	pK_i	30,59,114
⤷	pK_i 8.6 (K_i 2.4x10^-9 M) [30,59,114]
tolterodine		Hs	Antagonist	8.5 – 8.7	pK_i	43,114
⤷	pK_i 8.5 – 8.7 [43,114]
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.
oxybutynin		Rn	Antagonist	8.2	pK_i	94
⤷	pK_i 8.2 [94]
pirenzepine		Hs	Antagonist	7.8 – 8.3	pK_i	18,32,52,58,63,142
⤷	pK_i 7.8 – 8.3 [18,32,52,58,63,142]
hexahydrodifenidol		Rn	Antagonist	8.0	pK_i	18
⤷	pK_i 8.0 [18]
solifenacin		Rn	Antagonist	8.0	pK_i	94
⤷	pK_i 8.0 [94]
darifenacin		Hs	Antagonist	7.5 – 8.3	pK_i	43,52,56,59,114
⤷	pK_i 7.5 – 8.3 [43,52,56,59,114]
pirenzepine		Rn	Antagonist	7.8 – 7.9	pK_i	18,64
⤷	pK_i 7.8 – 7.9 [18,64]
amitriptyline		Hs	Antagonist	7.8	pK_i	118
⤷	pK_i 7.8 (K_i 1.47x10^-8 M) [118]
methoctramine		Rn	Antagonist	7.8	pK_i	18
⤷	pK_i 7.8 [18]
VU0255035		Hs	Antagonist	7.8	pK_i	112
⤷	pK_i 7.8 (K_i 1.487x10^-8 M) [112]
dosulepin		Hs	Antagonist	7.7	pK_i	118
⤷	pK_i 7.7 (K_i 1.8x10^-8 M) [118]
hexahydrosiladifenidol		Hs	Antagonist	7.7	pK_i	34
⤷	pK_i 7.7 [34]
hexahydrosiladifenidol		Rn	Antagonist	7.4 – 7.9	pK_i	18,64
⤷	pK_i 7.4 – 7.9 [18,64]
solifenacin		Hs	Antagonist	7.6	pK_i	59,114
⤷	pK_i 7.6 [59,114]
AFDX384		Hs	Antagonist	7.5	pK_i	32
⤷	pK_i 7.5 [32]
p-F-HHSiD		Hs	Antagonist	7.1 – 7.8	pK_i	34,58
⤷	pK_i 7.1 – 7.8 [34,58]
muscarinic toxin 1		Hs	Antagonist	7.3 – 7.6	pK_i	38,50
⤷	pK_i 7.3 – 7.6 [38,50]
guanylpirenzepine		Rn	Antagonist	7.3 – 7.6	pK_i	3,131
⤷	pK_i 7.3 – 7.6 [3,131]
AQ-RA 741		Hs	Antagonist	7.2 – 7.5	pK_i	32,43
⤷	pK_i 7.2 – 7.5 [32,43]
muscarinic toxin 3		Hs	Antagonist	7.1	pK_i	63
⤷	pK_i 7.1 [63]
BODIPY-pirenzepine		Hs	Antagonist	7.0	pK_i	60
⤷	pK_i 7.0 [60]
methoctramine		Hs	Antagonist	6.6 – 7.3	pK_i	32,34,52,115
⤷	pK_i 6.6 – 7.3 [32,34,52,115]
himbacine		Hs	Antagonist	6.7 – 7.1	pK_i	32,63,91
⤷	pK_i 6.7 – 7.1 [32,63,91]
(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	50
⤷	pK_i 6.4 [50]
otenzepad		Rn	Antagonist	5.9 – 6.3	pK_i	18,64
⤷	pK_i 5.9 – 6.3 [18,64]
lithocholylcholine		Rn	Antagonist	5.6	pK_i	24
⤷	pK_i 5.6 [24]
ML381		Hs	Antagonist	<5.0	pK_i	40
⤷	pK_i <5.0 (K_i >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

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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	1-2,22,82
⤷	pK_B 4.0 – 4.8 [1-2,22,82]
KT 5720		Hs	Positive	6.4	pK_d	77
⤷	pK_d 6.4 (K_d 3.98x10^-7 M) [77]
staurosporine		Hs	Positive	5.9	pK_d	77
⤷	pK_d 5.9 [77]
Gö 7874		Hs	Negative	5.8	pK_d	77
⤷	pK_d 5.8 [77]
WIN 51,708		Hs	Negative	5.8	pK_d	78
⤷	pK_d 5.8 [78]
KT 5823		Hs	Positive	5.7	pK_d	77
⤷	pK_d 5.7 [77]
WIN 62,577		Hs	Negative	5.5	pK_d	78
⤷	pK_d 5.5 [78]
brucine		Hs	Positive	4.5 – 5.8	pK_d	61,76
⤷	pK_d 4.5 – 5.8 (K_d 3x10^-5 – 1.78x10^-6 M) [61,76]
K-252a		Hs	Positive	5.1	pK_d	77
⤷	pK_d 5.1 [77]
vinburnine		Hs	Neutral	5.1	pK_d	61
⤷	pK_d 5.1 [61]
alcuronium		Hs	Negative	5.0	pK_d	61
⤷	pK_d 5.0 [61]
strychnine		Hs	Neutral	4.9 – 5.0	pK_d	61,73
⤷	pK_d 4.9 – 5.0 [61,73]
strychnine		Hs	Negative	4.9	pK_d	73
⤷	pK_d 4.9 [73]

M1 receptor

Contents:

M₁ receptor