M<sub>4</sub> receptor | Acetylcholine receptors (muscarinic) | IUPHAR/BPS Guide to PHARMACOLOGY

M4 receptor

Target id: 16

Nomenclature: M4 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 M4 receptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 479 11p12-p11.2 CHRM4 cholinergic receptor muscarinic 4 3,30
Mouse 7 479 2 E1 Chrm4 cholinergic receptor, muscarinic 4 51
Rat 7 478 3q32-q35 Chrm4 cholinergic receptor, muscarinic 4 39,78,91
Previous and Unofficial Names
HM3 [64-65] | Chrm-4 | cholinergic receptor, muscarinic 4 | cholinergic receptor
Database Links
Specialist databases
GPCRDB acm4_human (Hs), acm4_mouse (Mm)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium.
PDB Id:  5DSG
Ligand:  tiotropium
Resolution:  2.6Å
Species:  Human
References:  76
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
[3H]acetylcholine Hs Agonist 8.2 pKd 44
pKd 8.2 [44]
pentylthio-TZTP Hs Full agonist 8.7 pKi 37
pKi 8.7 [37]
NNC 11-1585 Hs Full agonist 8.6 pKi 13
pKi 8.6 [13]
NNC 11-1607 Hs Full agonist 8.1 pKi 13
pKi 8.1 [13]
xanomeline Hs Partial agonist 7.4 – 7.7 pKi 85,92
pKi 7.4 – 7.7 [85,92]
NNC 11-1314 Hs Full agonist 7.3 pKi 13
pKi 7.3 [13]
sabcomeline Hs Partial agonist 7.2 pKi 92
pKi 7.2 [92]
McN-A-343 Hs Partial agonist 5.6 – 6.7 pKi 41
pKi 5.6 – 6.7 [41]
cevimeline Hs Agonist 6.0 pKi 50
pKi 6.0 (Ki 1.012x10-6 M) [50]
Description: Displacement of [3H]QNB from cloned receptor.
arecaidine propargyl ester Hs Full agonist 5.9 pKi 37
pKi 5.9 [37]
methacholine Rn Agonist 5.8 pKi 63
pKi 5.8 (Ki 1.6x10-6 M) [63]
arecoline Hs Full agonist 5.5 pKi 37
pKi 5.5 [37]
milameline Hs Partial agonist 5.5 pKi 92
pKi 5.5 [92]
oxotremorine Hs Full agonist 5.2 pKi 37
pKi 5.2 [37]
oxotremorine-M Hs Full agonist 5.2 pKi 37
pKi 5.2 [37]
pilocarpine Hs Partial agonist 5.2 pKi 37
pKi 5.2 [37]
acetylcholine Hs Full agonist 4.5 – 5.6 pKi 10,37,43
pKi 4.5 – 5.6 [10,37,43]
methylfurmethide Hs Full agonist 4.7 pKi 37
pKi 4.7 [37]
carbachol Hs Full agonist 4.3 – 4.9 pKi 37,92
pKi 4.3 – 4.9 [37,92]
furtrethonium Hs Full agonist 4.3 pKi 37
pKi 4.3 [37]
bethanechol Hs Full agonist 4.0 pKi 37
pKi 4.0 [37]
(+)-aceclidine Hs Full agonist 5.4 pEC50 22
pEC50 5.4 [22]
(-)-aceclidine Hs Partial agonist 4.8 pEC50 22
pEC50 4.8 [22]
View species-specific agonist tables
Agonist Comments
The binding data for McN-A-343 [41] is found on rat striatum.
Please consult references [5,45,67,84] for further details of the activity of some of the ligands in this list.
McN-A-343 and pilocarpine have been found to be partial agonists [45] and full agonists [67,84] at the M4 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 9.7 – 10.5 pKd 14,65
pKd 9.7 – 10.5 (Kd 2x10-10 – 3.16x10-11 M) [14,65]
[3H]N-methyl scopolamine Hs Antagonist 9.9 – 10.2 pKd 8,10,14,34,37-38,40,43,60,84
pKd 9.9 – 10.2 (Kd 1.4x10-10 – 6x10-11 M) [8,10,14,34,37-38,40,43,60,84]
biperiden Hs Antagonist 8.6 pKd 2
pKd 8.6 (Kd 2.4x10-9 M) [2]
[3H]AF DX-384 Hs Antagonist 8.6 pKd 55
pKd 8.6 [55]
otenzepad Hs Antagonist 7.0 pKd 23
pKd 7.0 [23]
umeclidinium Hs Antagonist 10.3 pKi 69
pKi 10.3 [69]
propantheline Hs Antagonist 10.2 pKi 36
pKi 10.2 [36]
atropine Rn Antagonist 9.7 pKi 39
pKi 9.7 [39]
scopolamine Hs Antagonist 9.5 pKi 36
pKi 9.5 [36]
AE9C90CB Hs Antagonist 9.5 pKi 71
pKi 9.5 [71]
ipratropium Hs Antagonist 9.2 pKi 34
pKi 9.2 [34]
4-DAMP Rn Antagonist 9.1 pKi 39
pKi 9.1 [39]
atropine Hs Antagonist 8.7 – 9.5 pKi 6,34,36,65
pKi 8.7 – 9.5 [6,34,36,65]
4-DAMP Hs Antagonist 8.9 pKi 20
pKi 8.9 [20]
oxybutynin Hs Antagonist 8.7 pKi 71
pKi 8.7 [71]
silahexocyclium Hs Antagonist 8.5 pKi 6
pKi 8.5 [6]
tolterodine Hs Antagonist 8.3 – 8.4 pKi 27,71
pKi 8.3 – 8.4 [27,71]
UH-AH 37 Hs Antagonist 8.3 – 8.4 pKi 27,90
pKi 8.3 – 8.4 [27,90]
hexocyclium Hs Antagonist 8.3 pKi 6
pKi 8.3 [6]
amitriptyline Hs Antagonist 8.1 pKi 72
pKi 8.1 (Ki 7.2x10-9 M) [72]
himbacine Hs Antagonist 7.9 – 8.2 pKi 20,38,54
pKi 7.9 – 8.2 [20,38,54]
AFDX384 Hs Antagonist 8.0 pKi 20
pKi 8.0 [20]
AQ-RA 741 Hs Antagonist 7.8 – 8.2 pKi 20,27
pKi 7.8 – 8.2 [20,27]
tripitramine Hs Antagonist 7.9 pKi 56
pKi 7.9 [56]
darifenacin Hs Antagonist 7.3 – 8.1 pKi 27,33-34,71
pKi 7.3 – 8.1 [27,33-34,71]
hexahydrosiladifenidol Rn Antagonist 7.7 pKi 39
pKi 7.7 [39]
p-F-HHSiD Hs Antagonist 7.1 – 7.5 pKi 23,36
pKi 7.1 – 7.5 [23,36]
pirenzepine Hs Antagonist 7.0 – 7.6 pKi 20,33,36,38,90
pKi 7.0 – 7.6 [20,33,36,38,90]
dosulepin Hs Antagonist 7.2 pKi 72
pKi 7.2 (Ki 6.1x10-8 M) [72]
hexahydrosiladifenidol Hs Antagonist 6.5 – 7.7 pKi 6,23
pKi 6.5 – 7.7 [6,23]
muscarinic toxin 1 Hs Antagonist 7.1 pKi 31
pKi 7.1 [31]
hexahydrodifenidol Hs Antagonist 7.1 pKi 6
pKi 7.1 [6]
pirenzepine Rn Antagonist 7.1 pKi 39
pKi 7.1 [39]
methoctramine Hs Antagonist 6.6 – 7.5 pKi 6,20,23,33
pKi 6.6 – 7.5 [6,20,23,33]
solifenacin Hs Antagonist 6.8 pKi 71
pKi 6.8 [71]
otenzepad Rn Antagonist 6.5 pKi 39
pKi 6.5 [39]
guanylpirenzepine Rn Antagonist 6.2 pKi 83
pKi 6.2 [83]
muscarinic toxin 2 Hs Antagonist 5.9 pKi 31
pKi 5.9 [31]
VU0255035 Hs Antagonist 5.9 pKi 70
pKi 5.9 [70]
lithocholylcholine Hs Antagonist 5.3 pKi 10
pKi 5.3 [10]
muscarinic toxin 7 Hs Antagonist <5.0 pKi 57
pKi <5.0 [57]
ML381 Hs Antagonist >4.5 pKi 26
pKi >4.5 (Ki <3x10-5 M) [26]
glycopyrrolate Hs Antagonist 9.8 pIC50 74
pIC50 9.8 (IC50 1.58x10-10 M) [74]
Description: Assay uses glycopyrronium bromide
View species-specific antagonist tables
Antagonist Comments
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 [2].
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
KT 5720 Hs Neutral 6.4 pKd 47
pKd 6.4 [47]
WIN 51,708 Hs Negative 6.2 pKd 48
pKd 6.2 [48]
WIN 62,577 Hs Negative 5.9 pKd 48
pKd 5.9 [48]
Gö 7874 Hs Neutral 5.7 pKd 47
pKd 5.7 [47]
LY2119620 Hs Positive 5.7 pKd 16
pKd 5.7 [16]
alcuronium Hs Negative 5.6 pKd 37
pKd 5.6 [37]
brucine Hs Negative 4.7 – 6.0 pKd 37,46
pKd 4.7 – 6.0 [37,46]
staurosporine Hs Neutral 5.3 pKd 47
pKd 5.3 [47]
strychnine Hs Positive 4.8 – 5.0 pKd 37,43
pKd 4.8 – 5.0 [37,43]
vinburnine Hs Positive 4.6 pKd 37
pKd 4.6 [37]
N-benzyl brucine Hs Negative 4.5 pKd 46
pKd 4.5 [46]
N-benzyl brucine Hs Neutral 4.5 pKd 46
pKd 4.5 [46]
N-chloromethyl-brucine Hs Neutral 4.4 pKd 46
pKd 4.4 [46]
vincamine Hs Positive 4.2 pKd 37
pKd 4.2 [37]
thiochrome Hs Positive 4.0 pKd 44
pKd 4.0 [44]
brucine N-oxide Hs Neutral 3.6 pKd 46
pKd 3.6 [46]
brucine N-oxide Hs Positive 3.6 pKd 46
pKd 3.6 [46]
muscarinic toxin 3 Hs Negative 8.7 pKi 38,60
pKi 8.7 [38,60]
VU0152100 Rn Positive 6.4 pEC50 4
pEC50 6.4 (EC50 3.8x10-7 M) [4]
VU0152099 Rn Positive 6.4 pEC50 4
pEC50 6.4 (EC50 4.03x10-7 M) [4]
LY2033298 Hs Positive - - 9
[9]
VU0010010 Hs Positive - - 15
[15]
View species-specific allosteric modulator tables
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
References:  53,64
Tissue Distribution
Esophageal smooth muscle.
Species:  Human
Technique:  Radioligand binding.
References:  66
Bladder.
Species:  Human
Technique:  RT-PCR.
References:  79
CNS: forebrain.
Species:  Mouse
Technique:  immunocytochemistry.
References:  35
CNS: cerebral cortex, corpus striatum, thalamus, hypothalamus, pons-medulla.
Species:  Mouse
Technique:  Radioligand binding.
References:  58
Heart: intrinsic neurons.
Species:  Rat
Technique:  in situ hybridisation.
References:  32
CNS: basal forebrain, pedunculopontine and laterodorsal tegmental nuclei.
Species:  Rat
Technique:  in situ hybridisation.
References:  81
CNS: cerebral cortex, hippocampus, corpus striatum, olfactory tubercle, midbrain, pons-medulla, cerebellum.
Species:  Rat
Technique:  Immunoprecipitation.
References:  93
CNS: caudate putamen, nucleus accumbens, olfactory tubercle.
Species:  Rat
Technique:  in situ hybridisation.
References:  86
CNS: hippocampus.
Species:  Rat
Technique:  immunocytochemistry.
References:  49
Vestibular system.
Species:  Rat
Technique:  RT-PCR.
References:  82
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of IP1 levels in murine fibroblast cells (B82) transfected with the rat M4 receptor.
Species:  Rat
Tissue:  B82 cells.
Response measured:  Stimulation of IP1 accumulation.
References:  39
Measurement of cAMP levels in murine fibroblast cells (B82) transfected with the rat M4 receptor.
Species:  Rat
Tissue:  B82 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  39
Measurement of cAMP levels in JEG-3 cells transfected with the human M2 receptor, using a cAMP response element (CRE)-coupled luciferase construct as the reporter.
Species:  Human
Tissue:  JEG-3 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  53
Measurement of cAMP levels in CHO cells transfected with the human M4 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  13
Measurement of ERK1/2 activity in COS-7 cells transfected with the human M4 receptor.
Species:  Human
Tissue:  COS-7 cells.
Response measured:  Increase in ERK1/2 activity.
References:  68
Measurement of Ca2+ channel activity in rat superior cervical ganglion neurons endogenously expressing the M4 receptor.
Species:  Rat
Tissue:  Superior cervical ganglion neurons.
Response measured:  Inhibition of Ca2+ channels.
References:  24-25
Measurement of AC activity in rat striatal homogenates endogenously expressing the M4 receptor.
Species:  Rat
Tissue:  Corpus striatum.
Response measured:  Inhibition of AC activity.
References:  21,59
Measurement of the effects of a ligand on the level, or rate, of binding of GTPγ35S to membranes.
Species:  Human
Tissue:  CHO cells.
Response measured:  The binding of GTPγ35S to G proteins coupled to the receptor.
References:  1,42-45,47-48
Measurement of the effects of a ligand on the rate of hydrolysis of GTP by G proteins in membranes.
Species:  Human
Tissue:  CHO cell membranes.
Response measured:  Generation of 32Pi from [γ-32P]GTP.
References:  1,45
Physiological Functions
Autoreceptor: modulation of acetylcholine release.
Species:  Rat
Tissue:  Urinary bladder.
References:  17
Autoreceptor: modulation of acetylcholine release.
Species:  Human
Tissue:  Urinary bladder detrusor muscle.
References:  18
Contraction.
Species:  Rat
Tissue:  Urinary bladder detrusor muscle.
References:  62
Inhibition of dopaminergic (D1 receptor) signalling.
Species:  Rat
Tissue:  Nucleus accumbens.
References:  61
Cell migration.
Species:  Human
Tissue:  Keratinocytes.
References:  12
Physiological Consequences of Altering Gene Expression
M4 receptor knockout mice exhibit an increase in anxiolysis compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  19
Hippocampal, cortical and striatal brain slices from M2/M4 double knockout mice lack muscarinic agonist-induced inhibition of acetylcholine release that is seen with wild-type brain slices.
Striatal slices from M4 receptor single knockout mice exhibit the same loss of inhibition of acetylcholine release, but the inhibition remains intact in the hippocampal and cortical slices.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  94
Smooth muscle preparations (gallbladder) from M4 receptor knockout mice exhibit reduced agonist-induced contractions compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  73
Vas deferens tissue from M4 receptor knockout mice exhibits reduced agonist-induced inhibition of noradrenaline release compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  77
Striatal slices from M4 receptor knockout mice exhibit abolished agonist-induced potentiation of dopamine release.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  95
M4 receptor knockout mice exhibit enhanced dopaminergic locomotor activity.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  28-29
Epidermal keratinocytes from M4 receptor knockout mice exhibit reduced agonist-induced migration compared to keratinocytes from wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  12
M4 receptor knockout mice exhibit increased basal hippocampal acetylcholine levels compared to wild-type mice.
M2/M4 double knockout mice exhibit a further increase in basal acetylcholine levels.
In addition, M4 and M2/M4 knockout mice exhibit an increase in hippocampal acetylcholine release in response to a novel environment.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  80
M4 receptor knockout mice exhibit a significantly reduced wound epithelialisation rate compared to wild-type mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  11
Smooth muscle from the small intestine of M4 receptor knockout mice do not exhibit any alteration in EFS-induced acetylcholine release.
However, M2/M4 double knockout mice exhibit an increase in acetylcholine release.
Overall, it is thought that both M2 and M4 receptors mediate the autoinhibitory control of acetylcholine release in the mouse ileum, and that each can compensate for loss of the other.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  75
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Chrm4tm1Minm Chrm4tm1Minm/Chrm4tm1Minm
involves: 129X1/SvJ * DBA/2J
MGI:88399  MP:0009745 abnormal behavioral response to xenobiotic PMID: 12729838 
Chrm2tm1Jwe|Chrm4tm1Jwe Chrm2tm1Jwe/Chrm2tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S4/SvJae * 129S6/SvEvTac * CF-1
MGI:88397  MGI:88399  MP:0004994 abnormal brain wave pattern PMID: 16110248 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0002206 abnormal CNS synaptic transmission PMID: 15919709 
Chrm1tm1Jwe|Chrm4tm1Jwe Chrm1tm1Jwe/Chrm1tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88396  MGI:88399  MP:0002206 abnormal CNS synaptic transmission PMID: 15919709 
Chrm2tm1Jwe|Chrm4tm1Jwe Chrm2tm1Jwe/Chrm2tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S4/SvJae * 129S6/SvEvTac * CF-1
MGI:88397  MGI:88399  MP:0002206 abnormal CNS synaptic transmission PMID: 15919709 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0005085 abnormal gallbladder physiology PMID: 11961069 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0001629 abnormal heart rate PMID: 10688600 
Chrm4tm1Minm Chrm4tm1Minm/Chrm4tm1Minm
involves: 129X1/SvJ * DBA/2J
MGI:88399  MP:0001392 abnormal locomotor activity PMID: 12729838 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0004811 abnormal neuron physiology PMID: 20147565 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
B6.129S6-Chrm4
MGI:88399  MP:0001529 abnormal vocalization PMID: 18382674 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0002822 catalepsy PMID: 20147565 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0001262 decreased body weight PMID: 10468635 
Chrm1tm1Jwe|Chrm4tm1Jwe Chrm1tm1Jwe/Chrm1tm1Jwe,Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88396  MGI:88399  MP:0002917 decreased synaptic depression PMID: 15919709 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0009749 enhanced behavioral response to addictive substance PMID: 20147565 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0009754 enhanced behavioral response to cocaine PMID: 20147565 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0009746 enhanced behavioral response to xenobiotic PMID: 20147565 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0001399 hyperactivity PMID: 10468635 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0001399 hyperactivity PMID: 20147565 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0009747 impaired behavioral response to xenobiotic PMID: 20147565 
Chrm4tm1Jwe Chrm4tm1Jwe/Chrm4tm1Jwe
involves: 129S6/SvEvTac * CF-1
MGI:88399  MP:0000740 impaired smooth muscle contractility PMID: 11961069 
Chrm4tm2.1Jwe|Tg(Drd1a-cre)AGsc Chrm4tm2.1Jwe/Chrm4tm2.1Jwe,Tg(Drd1a-cre)AGsc/0
involves: 129S6/SvEvTac * C57BL/6 * FVB/N
MGI:3761815  MGI:88399  MP:0001906 increased dopamine level PMID: 20147565 
General Comments
For reviews on muscarinic receptor knockout mice see [7,52,87-89].

References

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1. Birdsall NJM, Farries T, Gharagozloo P, Kobayashi S, Lazareno S, Sugimoto M. (1999) Subtype selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: functional studies. Mol. Pharmacol., 55: 778-786. [PMID:10101037]

2. Bolden C, Cusack B, Richelson E. (1992) Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. J. Pharmacol. Exp. Ther., 260 (2): 576-80. [PMID:1346637]

3. Bonner TI, Modi WS, Seuanez HN, O'Brien SJ. (1991) Chromosomal mapping of the five human genes encoding muscarinic acetylcholine receptors. Cytogenet. Cell Genet., 58: 1850-1851.

4. Brady AE, Jones CK, Bridges TM, Kennedy JP, Thompson AD, Heiman JU, Breininger ML, Gentry PR, Yin H, Jadhav SB et al.. (2008) Centrally active allosteric potentiators of the M4 muscarinic acetylcholine receptor reverse amphetamine-induced hyperlocomotor activity in rats. J. Pharmacol. Exp. Ther., 327 (3): 941-53. [PMID:18772318]

5. Bräuner-Osborne H, Ebert B, Brann MR, Falch E, Krogsgaard-Larsen P. (1996) Functional partial agonism at cloned human muscarinic acetylcholine receptors. Eur J Pharmacol, 313: 145-150. [PMID:8905341]

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Nigel J. M. Birdsall, David A. Brown, Noel J. Buckley, Arthur Christopoulos, Richard M. Eglen, Frederick Ehlert, Rudolf Hammer, Heinz J. Kilbinger, Günter Lambrecht, Fred Mitchelson, Ernst Mutschler, Neil M. Nathanson, Roy D. Schwarz, Andrew B. Tobin, Jurgen Wess.
Acetylcholine receptors (muscarinic): M4 receptor. Last modified on 13/07/2018. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=16.