The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

It is located in the brain, spleen, and lymphocytes of lymph nodes where activation yields post- and 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 neurons of the guinea-pig ileum.

Medical relevance The Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and Alzheimer's disease.

The α7 receptor is highly implicated in the efficacy of Varenicline for smoking cessation therapy significantly more than α4β2 which is responsible for Nicotine's rewarding effects. Upregulation 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.

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

Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.

α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis. α7 receptors are also involved in angiogenic and neurogenic activity, and have anti-apoptotic effects.

Ligands

Agonists

(+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan- 2-carboxamide: potent and highly subtype-selective A-582941: partial agonist; activates ERK1/2 and CREB phosphorylation; enhances cognitive performance ABT-107Bitner RS, Bunnelle WH, Decker MW, Drescher KU, Kohlhaas KL, Markosyan S, Marsh KC, Nikkel AL, Browman K, Radek R, Anderson DJ, Buccafusco J, Gopalakrishnan M. In vivo pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107: preclinical considerations in Alzheimer's disease. J Pharmacol Exp Ther. 2010 Sep 1;334(3):875-86. AQW-051 AR-R17779: full agonist, nootropic Amyloid beta: neurotoxic marker of Alzheimer's disease TC-1698: subtype-selective; neuroprotective effects via activation of the JAK2/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 PHA-709829: potent and subtype-selective; robust in vivo efficacy in a rat auditory sensory gating model Analogues: improved hERG safety profile over PNU-282,987 SSR-180,711: partial agonist Tilorone Tropisetron: subtype-selective partial agonist; 5-HT3 receptor antagonist WAY-317,538 — selective potent full agonist with nootropic and neuroprotective properties Anabasine Acetylcholine Nicotine Varenicline Epiboxidine Choline 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

Other Nefiracetam Aspirin

Antagonists It is found that anandamide and ethanol cause an additive inhibition on the function of α7-receptor by interacting with distinct regions of the receptor. Although ethanol inhibition of the α7-receptor is likely to involve the N-terminal region of the receptor, the site of action for anandamide is located in the transmembrane and carboxyl-terminal domains of the receptors. Anandamide α-Bungarotoxin α-Conotoxin ArIB[V11L,V16D]: potent and highly subtype-selective; slowly reversible β-Caryophyllene Bupropion (very weakly) Dehydronorketamine Dextroamphetamine (very weakly) Ethanol Hydroxybupropion (very weakly) Kynurenic acid Levoamphetamine (very weakly) Memantine Lobeline Methyllycaconitine Norketamine Quinolizidine (−)-1-epi-207I: α7 subtype preferring blocker

Negative allosteric modulators (NAMs)

Hydroxynorketamine

See also α3β2-Nicotinic receptor α3β4-Nicotinic receptor α4β2-Nicotinic receptor RIC3, a chaperone protein for α7 receptors Endocannabinoids

References