The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric .e., (α7)₅ stoichiometry">stoichiometry.html" ;"title=".e., (α7)₅ stoichiometry">.e., (α7)₅ stoichiometry It is located in the brain, spleen, and lymphocytes of lymph nodes where activation yields Excitatory postsynaptic potential, post- and excitatory presynaptic potential, presynaptic excitation, mainly by increased Ca²⁺ permeability. Further, recent work has implicated this receptor as being important for generation of adult mammal neurons in the retina. Functional α7 receptors are present in the

submucous plexus The submucosal plexus (Meissner's plexus, plexus of the submucosa, plexus submucosus) lies in the submucosa of the intestinal wall. The nerves of this plexus are derived from the myenteric plexus which itself is derived from the plexuses of para ...

neurons of the guinea-pig

ileum The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may ...

Medical relevance

The Recent work has demonstrated a potential role in reducing inflammatory

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...

, and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

. The α7 receptor is highly implicated in the efficacy of

Varenicline Varenicline, sold under the brand names Chantix and Champix among others, is a medication used for smoking cessation and for the treatment of dry eye syndrome. It is a nicotinic acetylcholine receptor partial agonist. When activated, this recep ...

for smoking cessation therapy significantly more than

α4β2 The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of nicotinic acetylcholine receptor implicated in learning, consisting of α4 and β2 subunits. It is located in the brain, where activation yields post- and pr ...

which is responsible for Nicotine's rewarding effects.

Upregulation In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as R ...

of α7-nAChR's is greatly correlated with a stronger response. An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. Activation of α7 nicotinic acetylcholine receptor on mast cells, is a mechanism by which nicotine enhances atherosclerosis. Both

and α7

nicotinic receptors Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

appear to be critical for

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

working memory Working memory is a cognitive system with a limited capacity that can Memory, hold information temporarily. It is important for reasoning and the guidance of decision-making and behavior. Working memory is often used synonymously with short-term m ...

learning Learning is the process of acquiring new understanding, knowledge, behaviors, skills, value (personal and cultural), values, Attitude (psychology), attitudes, and preferences. The ability to learn is possessed by humans, non-human animals, and ...

, and

attention Attention or focus, is the concentration of awareness on some phenomenon to the exclusion of other stimuli. It is the selective concentration on discrete information, either subjectively or objectively. William James (1890) wrote that "Atte ...

. α7-nicotinic receptors also appear to be involved in

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

progression. They have been shown to mediate cancer

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...

and

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

. α7 receptors are also involved in

angiogenic Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and s ...

and neurogenic activity, and have anti-

apoptotic Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemical events lead to characteristic cell changes ( morphology) and death. These ...

effects.

Ligands

Agonists

* (+)-''N''-(1-azabicyclo .2.2ct-3-yl)benzo 'b''uran- 2-carboxamide: potent and highly subtype-selective * Tilorone. * A-582941: partial agonist; activates

ERK1 Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the ''MAPK3'' gene. Function The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) fami ...

/ 2 and

CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

; enhances cognitive performance * AR-R17779: full agonist, nootropic *

Amyloid beta Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...

: neurotoxic marker of

* TC-1698: subtype-selective; neuroprotective effects via activation of the

JAK2 Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF ...

/ PI-3K cascade, neutralized by angiotensin II AT(2) receptor activation * Bradanicline — partial agonist, in development for treatment of schizophrenia * Encenicline — partial agonist with nootropic properties, in development for treatment of schizophrenia and Alzheimer's disease * GTS-21 — partial agonist, in development for treatment of schizophrenia and/or Alzheimer's disease * PHA-543,613 — selective and potent agonist with nootropic properties * PNU-282,987 — selective and potent agonist, but may cause

long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainti ...

* PHA-709829: potent and subtype-selective; robust in vivo efficacy in a rat auditory sensory gating model ** Analogues: improved

hERG hERG (the human '' Ether-à-go-go''-Related Gene) is a gene () that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel (sometimes simply denoted as 'hERG') is best known for its contribution t ...

safety profile over PNU-282,987 * SSR-180,711: partial agonist *

Tropisetron Tropisetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy, although it has been used experimentally as an analgesic in cases of fibromyalgia. It was patented in 198 ...

: subtype-selective partial agonist; 5-HT₃ receptor antagonist * WAY-317,538 — selective potent full agonist with nootropic and neuroprotective properties *

Anabasine Anabasine is a pyridine and piperidine alkaloid found in the tree tobacco ('' Nicotiana glauca'') plant, as well as in tree tobacco's close relative the common tobacco plant ('' Nicotiana tabacum''). It is a structural isomer of, and chemically ...

Acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

Epiboxidine Epiboxidine is a chemical compound which acts as a partial agonist at neural nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes. It was developed as a less toxic analogue of the potent frog-derived alkaloid ...

Choline Choline is a cation with the chemical formula . Choline forms various Salt (chemistry), salts, such as choline chloride and choline bitartrate. An essential nutrient for animals, it is a structural component of phospholipids and cell membrane ...

* ICH-3: subtype-selective partial agonist

Positive allosteric modulators (PAMs)

At least two types of positive allosteric modulators (PAMs) can be distinguished. * PNU-120,596 *NS-1738: marginal effects on α₇ desensitization kinetics; modestly brain-penetrant * AVL-3288: unlike the above PAMs, AVL-3288 does not affect α₇ desensitization kinetics, and is readily brain penetrant. Improves cognitive behavior in animal models In clinical development for cognitive deficits in schizophrenia. * A-867744 *

Ivermectin Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice ...

Other

Nefiracetam Nefiracetam is a nootropic drug of the racetam family. Preliminary research suggests that it may possess certain antidementia properties in rats. Effects Nefiracetam's cytoprotective actions are mediated by enhancement of GABAergic, cholinergi ...

Antagonists

It is found that

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

and ethanol cause an additive inhibition on the function of α₇-receptor by interacting with distinct regions of the receptor. Although

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

inhibition of the α₇-receptor is likely to involve the

N-terminal The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

region of the receptor, the site of action for anandamide is located in the

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

and

carboxyl-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

domains of the receptors. *

Anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

* α-Bungarotoxin * α-

Conotoxin A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus '' Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. C ...

ArIB 11L,V16D potent and highly subtype-selective; slowly reversible *

β-Caryophyllene Caryophyllene (), more formally (−)-β-caryophyllene (BCP), is a natural bicyclic sesquiterpene that occurs widely in nature. Caryophyllene is notable for having a cyclobutane ring, as well as a ''trans''-double bond in a 9-membered ring, both ...

Bupropion Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder, seasonal affective disorder, and to support smo ...

(very weakly) *

Dehydronorketamine Dehydronorketamine (DHNK), or 5,6-dehydronorketamine, is a minor metabolite of ketamine which is formed by dehydrogenation of its metabolite norketamine. Though originally considered to be inactive, DHNK has been found to act as a potent and sele ...

Dextroamphetamine Dextroamphetamine (international nonproprietary name, INN: dexamfetamine) is a potent central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narc ...

Ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

Hydroxybupropion Hydroxybupropion (code name BW 306U), or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. It is formed from bupropion by the liver enzyme CYP2B6 during first-pass metabolism. With oral ...

(very weakly) *

Kynurenic acid Kynurenic acid (KYNA or KYN) is a product of the normal metabolism of amino acid -tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an ...

Levoamphetamine Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination drug, combination with dextroam ...

(very weakly) *

Memantine Memantine, sold under the brand name Namenda among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth. Common side effects include headache, constipation, sleepiness, and dizz ...

Lobeline Lobeline is a piperidine alkaloid found in a variety of plants, particularly those in the genus '' Lobelia'', including Indian tobacco ('' Lobelia inflata''), Devil's tobacco ('' Lobelia tupa''), great lobelia ('' Lobelia siphilitica''), '' Lobe ...

* Methyllycaconitine *

Norketamine Norketamine, or ''N''-desmethylketamine, is the major active metabolite of ketamine, which is formed mainly by CYP3A4. Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist, but is about 3–5 times less potent as ...

* Quinolizidine (−)-1-epi-207I: α₇ subtype preferring blocker

Negative allosteric modulators (NAMs)

Hydroxynorketamine Hydroxynorketamine (HNK), or 6-hydroxynorketamine, is a minor metabolite of the anesthetic, dissociative, and antidepressant drug ketamine. It is formed by hydroxylation of the intermediate norketamine, another metabolite of ketamine. As of lat ...

References

{{DEFAULTSORT:Alpha-7 Nicotinic Receptor Nicotinic acetylcholine receptors Ion channels

Medical relevance

Ligands

Agonists

Positive allosteric modulators (PAMs)

Other

Antagonists

Negative allosteric modulators (NAMs)

See also

References