nicotinic acetylcholine receptor α7 subunit | Nicotinic acetylcholine receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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nicotinic acetylcholine receptor α7 subunit

target has curated data in GtoImmuPdb

Target id: 468

Nomenclature: nicotinic acetylcholine receptor α7 subunit

Family: Nicotinic acetylcholine receptors

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
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 502 15q14 CHRNA7 cholinergic receptor nicotinic alpha 7 subunit 10
Mouse 4 502 7 C Chrna7 cholinergic receptor, nicotinic, alpha polypeptide 7 41
Rat 4 502 1q22 Chrna7 cholinergic receptor nicotinic alpha 7 subunit 47
Previous and Unofficial Names
nAChRa7 | NARAD | neuronal acetylcholine receptor subunit alpha-7 | Acra7 | cholinergic receptor, nicotinic, alpha 7 (neuronal) | cholinergic receptor, nicotinic alpha 7 | cholinergic receptor
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Functional Characteristics
PCa/PNa = 6.6-20, Pf = 8.8 - 11.4%
Natural/Endogenous Ligands
Commonly used antagonists (Human)
(α7)5: DHβE (IC50 = 8 - 20 μM); (α7)5: tubocurarine (IC50 = 3.1 μM)

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]epibatidine Hs Full agonist 12.2 pKd
pKd 12.2 (Kd 6x10-13 M) (α7)5
[3H]A-585539 Hs Full agonist 10.1 pKd 2
pKd 10.1 (Kd 7x10-11 M) native α7 [2]
[3H]AZ11637326 Hs Full agonist 9.6 pKd 20
pKd 9.6 (Kd 2.3x10-10 M) (α7)5 [20]
AZD0328 Hs Full agonist 8.5 pKi 37
pKi 8.5 (Ki 3x10-9 M) [37]
encenicline Hs Partial agonist 8.4 pKi 37-38
pKi 8.4 (Ki 4.3x10-9 M) [37-38]
AQW051 Hs Agonist 7.6 pKi 27
pKi 7.6 (Ki 2.7x10-8 M) [125I]α- bungarotoxin binding assay [27]
PSAB-OFP Hs Full agonist 5.7 pEC50 6
pEC50 5.7 (EC50 2.2x10-6 M) [6]
4BP-TQS Hs Full agonist - - 19
allosteric [19]
bradanicline Hs Full agonist - - 24
(α7)5 [24]
PNU-282987 Hs Full agonist - - 5
(α7)5 [5]
A-582941 Hs Full agonist - - 4
(α7)5 [4]
PHA-709829 Hs Full agonist - - 1
(α7)5 [1]
PHA-543613 Hs Full agonist - - 51
(α7)5 [51]
Agonist Comments
EVP-6124 shows selectivity for α7 nAChRs and does not activate or inhibit heteromeric α4β2 nAChRs [43].
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]α-bungarotoxin Hs Antagonist 8.3 – 9.1 pKd
pKd 8.3 – 9.1 (Kd 5x10-9 – 7x10-10 M) (α7)5
[3H]α-bungarotoxin Hs Antagonist 8.3 – 9.1 pKd
pKd 8.3 – 9.1 (Kd 5x10-9 – 7x10-10 M) (α7)5
[3H]methyllycaconitine Rn Antagonist 8.7 pKd
pKd 8.7 (Kd 1.9x10-9 M) native α7*
atracurium Hs Antagonist 7.9 – 8.3 pIC50 28
pIC50 7.9 – 8.3 (IC50 1.3x10-8 – 5.6x10-9 M) [28]
Description: Antagonism of ACh activation of human α7 nACh receptors expressed in Xenopus oocytes, at different ACh concentrations.
α-bungarotoxin Hs Antagonist - -
α-conotoxin ImI Hs Antagonist - -
methyllycaconitine Hs Antagonist - -
α-conotoxin ArIB Hs Antagonist - -
View species-specific antagonist tables
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Use-dependent Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
mecamylamine Hs - no 4.8 pIC50 - no
pIC50 4.8 (IC50 1.56x10-5 M) (α7)5
Not voltage dependent
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
BNC375 Rn Positive 5.7 pEC50 - no 23
pEC50 5.7 (EC50 1.9x10-6 M) [23]
Not voltage dependent
BNC375 Hs Positive 5.6 pEC50 - no 50
pEC50 5.6 (EC50 2.64x10-6 M) [50]
Not voltage dependent
ivermectin Hs Positive 5.1 pEC50 - no 29
pEC50 5.1 (EC50 9x10-6 M) [29]
Not voltage dependent
JNJ1930942 Hs Positive - - - no 12
(α7)5:Type 1/2 [12]
Not voltage dependent
A-867744 Hs Positive - - - no 34
(α7)5:Type 2; also blocks α3β4 and α4β2 [34]
Not voltage dependent
PNU-120596 Hs Positive - - - no 26
(α7)5:Type 2 [26]
Not voltage dependent
LY2087101 Hs Positive - - - no 7
(α7)5:Type 1 [7]
Not voltage dependent
NS1738 Hs Positive - - - no 48
(α7)5:Type 1; also blocks α3β4 and α4β2 [48]
Not voltage dependent
View species-specific allosteric modulator tables
Immunopharmacology Comments
Included in Guide to Immunopharmacology as CHRNA7 knockout aggravates rheumatoid arthritis in mice [49].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0032691 negative regulation of interleukin-1 beta production IMP
GO:0032715 negative regulation of interleukin-6 production IMP
GO:0032720 negative regulation of tumor necrosis factor production IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0050727 regulation of inflammatory response IMP
GO:0050728 negative regulation of inflammatory response IMP
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0006897 endocytosis IMP
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0042113 B cell activation IMP
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0042110 T cell activation IMP
GO:0042113 B cell activation IMP
Immuno Process:  Inflammation
GO Annotations:  Associated to 2 GO processes
GO:0050727 regulation of inflammatory response IMP
GO:0050728 negative regulation of inflammatory response IMP
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0042110 T cell activation IMP
Tissue Distribution
High levels of α7 mRNA are expressed in the dentate granular layer and CA2/CA3 region of the hippocampus, in the caudate nucleus, and in the pulvinar and ventroposterolateral nuclei of the thalamus. [125I]α-bungarotoxin binding is very high in the hippocampus and in the pyramidal cells of the CA1 region, but is relatively low in the subicular complex.
Expression level:  High
Species:  Human
Technique:  in situ hybridisation, Radioligand binding.
References:  45
Expression in mouse brain is similar to that reported in rat, with strong expression in the hippocampus, amygdala, several hypothalamic nuclei, cerebral cortex, lateral areas of the interpeduncular nucleus, medial habenula and inferior colliculus. In contrast to rat brain, significant labeling of caudate putamen was observed.
Expression level:  High
Species:  Mouse
Technique:  in situ hybridisation
References:  35
The regional distribution of [125I]α-bungarotoxin binding is similar to that in rat brain. However, unlike in rat brain there is a significant signal in the olfactory tubercle, the nucleus accumbens and the caudate putamen. The binding sites for [125I]α-bungarotoxin are eliminated from all brain areas in α7 knockout mice.
Species:  Mouse
Technique:  Radioligand binding.
References:  40,42
High levels of α7 subunit mRNA are expressed in hippocampal cell layers, superficial and deep layers of the cerebral cortex, several hypothalamic nuclei, olfactory cortex, inferior colliculus and medial septum. Expression also occurs in the inferior colliculus, medial habenula and interpeduncular nucleus.
Species:  Rat
Technique:  in situ hybridisation
References:  47
High levels of [125I]α-bungarotoxin binding are detected in the accessory olfactory bulb, deep cortical layers, thehippocampus (particularly the stratum oriens, and the dentate and CA3 regions), the amygdala, hypothalamic nuclei, the subthalamic nucleus, the ventrolateral geniculate nucleus, the superior and inferior colliculus, and several pontine nuclei. Very little specific labeling is observed in the nucleus accumbens, caudate putamen and most thalamic nuclei
Expression level:  High
Species:  Rat
Technique:  Radioligand binding.
References:  3,13,25,46
Tissue Distribution Comments
For expression profiles in other primates see:-
Cynomologous monkey [11], Rhesus monkey [21-22,31], Macaca cynomologous Monkey[30], and Squirrel monkey [44]
Physiological Consequences of Altering Gene Expression
Knockout mice have been reported to have reduced cognitive deficits in a model of Alzheimer's disease.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  14
Knockout mice have been reported to have an increased incidence and severity of rheumatoid arthritis.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  49
Mice expressing α7 containing the L247T mutation in the second transmembrane domain die within a day of birth. Extensive apoptosis is observed in these mutant mice. Heterozygotes are viable but are more sensitive to nicotine-induced seizures.
Species:  Mouse
Tissue:  in vivo
Technique:  Transgensis
References:  8,39
Impaired passive avoidance learning is observed in mice lacking both the α7 and β2 subunits.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  36
Knockout mice are viable and anatomically normal but lack high-affinity α-bungarotoxin binding sites in the brain and lack rapidly desensitizing nicotinic currents in hippocampal neurons. Other effects that have been reported include: reduced neuroprotective effects of nicotine in hippocampal neurons and reduced maturation and integration of adult-born neurons in the hippocampus; cognitive deficits; impaired attention and spatial learning.
Species:  Mouse
Tissue:  in vivo
Technique:  Knockout
References:  9,15-16,33,39,52
Clinically-Relevant Mutations and Pathophysiology
Disease:  Chromosome 15q13.3 deletion syndrome
Synonyms: 15q13.3 microdeletion syndrome [Orphanet: ORPHA199318]
Chromosome 15q13.3 microdeletion syndrome
OMIM: 612001
Orphanet: ORPHA199318
Disease:  Schizophrenia 13; SCZD13
Synonyms: Schizophrenia [Orphanet: ORPHA3140] [OMIM: 181500] [Disease Ontology: DOID:5419]
Disease Ontology: DOID:5419
OMIM: 181500, 613025
Orphanet: ORPHA3140
References:  17,32
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Partial gene duplication Human - Chromosome 15 18
Polymorphism Human - Promoter 32
Gene Expression and Pathophysiology
Tissue or cell type:  Brain
Pathophysiology:  Schizophrenia
Species:  Human
Technique:  Post-mortem radioligand binding
References:  17


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23. Harvey AJ, Avery TD, Schaeffer L, Joseph C, Huff BC, Singh R, Morice C, Giethlen B, Grishin AA, Coles CJ et al.. (2019) Discovery of BNC375, a Potent, Selective, and Orally Available Type I Positive Allosteric Modulator of α7 nAChRs. ACS Med Chem Lett, 10 (5): 754-760. [PMID:31097995]

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48. Timmermann DB, Grønlien JH, Kohlhaas KL, Nielsen EØ, Dam E, Jørgensen TD, Ahring PK, Peters D, Holst D, Christensen JK et al.. (2007) An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J. Pharmacol. Exp. Ther., 323 (1): 294-307. [PMID:17625074]

49. van Maanen MA, Stoof SP, Larosa GJ, Vervoordeldonk MJ, Tak PP. (2010) Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis in nicotinic acetylcholine receptor alpha7 subunit gene knockout mice. Ann. Rheum. Dis., 69 (9): 1717-23. [PMID:20511609]

50. Wang X, Daley C, Gakhar V, Lange HS, Vardigan JD, Pearson M, Zhou X, Warren L, Miller CO, Belden M et al.. (2020) Pharmacological Characterization of the Novel and Selective α7 Nicotinic Acetylcholine Receptor-Positive Allosteric Modulator BNC375. J. Pharmacol. Exp. Ther., 373 (2): 311-324. [PMID:32094294]

51. Wishka DG, Walker DP, Yates KM, Reitz SC, Jia S, Myers JK, Olson KL, Jacobsen EJ, Wolfe ML, Groppi VE et al.. (2006) Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an agonist of the alpha7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: synthesis and structure--activity relationship. J. Med. Chem., 49 (14): 4425-36. [PMID:16821801]

52. Young JW, Crawford N, Kelly JS, Kerr LE, Marston HM, Spratt C, Finlayson K, Sharkey J. (2007) Impaired attention is central to the cognitive deficits observed in alpha 7 deficient mice. Eur Neuropsychopharmacol, 17 (2): 145-55. [PMID:16650968]


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