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

subunit Subunit may refer to: *Subunit HIV vaccine, a class of HIV vaccine *Protein subunit, a protein molecule that assembles with other protein molecules *Monomer, a molecule that may bind chemically to other molecules to form a polymer *Sub-subunit, a ...

s. It is located in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

, where activation yields

post- ''Post-'' (stylized in all caps In typography, all caps (short for "all capitals") refers to text or a font in which all letters are capital letters, for example: "THIS TEXT IS IN ALL CAPS". All caps may be used for emphasis (for a word ...

and presynaptic excitation, mainly by increased Na⁺ and K⁺ permeability. Stimulation of this receptor subtype is also associated with

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...

secretion. People with the inactive CHRNA4 mutation Ser248Phe are an average of 10 cm (4 inches) shorter than average and predisposed to

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

. A 2015 review noted that stimulation of the α4β2 nicotinic receptor in the brain is responsible for certain improvements in attentional performance; among the nicotinic receptor subtypes,

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 ...

has the highest

binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mol ...

at the α4β2 receptor (k_i=1 ), which is also the primary biological target that mediates nicotine's

addictive Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use oft ...

properties. The receptors exist in the two stoichiometries: *(α4)₂(β2)₃ receptors have high sensitivity to

and low Ca²⁺ permeability (HS receptors) *(α4)₃(β2)₂ receptors have low sensitivity to nicotine and high Ca²⁺ permeability (LS receptors)

Structure

The α4β2 receptor assemble in two distinct stoichiometric forms. One stoichiometry contains three α4 and two β2 subunits (α4)₃(β2)₂ whereas the other stoichiometry contains two α4 and three β2 (α4)₂(β2)₃ The x-ray structure of the (α4)₂(β2)₃ receptor is known since 2016 and reveals a circular α–β–β–α–β ordering of subunits.

Ligands

Agonists

3-Bromocytisine 3-Bromocytisine is a derivative of the toxic alkaloid cytisine that acts as a highly potent agonist at neural nicotinic acetylcholine receptors, binding primarily to the α4β2 and α7 subtypes. 3-Bromocytisine is a full agonist at the α7 subty ...

Acetylcholine Acetylcholine (ACh) is an organic chemical 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. Part ...

Cytisine Cytisine, also known as baptitoxine, cytisinicline, or sophorine, is an alkaloid that occurs naturally in several plant genera, such as ''Laburnum'' and ''Cytisus'' of the family Fabaceae. It has been used medically to help with smoking cessati ...

* Galantamine *

Epibatidine Epibatidine is a chlorinated alkaloid that is secreted by the Ecuadoran frog '' Epipedobates anthonyi'' and poison dart frogs from the Ameerega genus. It was discovered by John W. Daly in 1974, but its structure was not fully elucidated until ...

* Epiboxidine *

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 ...

* A-84,543 * A-366,833 * ABT-418 * Arecoline * Altinicline * Dianicline * Ispronicline *

Pozanicline Pozanicline (INN, codenamed ABT-089) is a drug developed by Abbott, that has nootropic and neuroprotective effects. Animal studies suggested it useful for the treatment of ADHD and subsequent human trials have shown ABT-089 to be effective for t ...

* Rivanicline *

Tebanicline Tebanicline (ebanicline, ABT-594) is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analog of the potent poison dart frog-derived compound epibatidine, which is about 200 times stron ...

TC-1827 TC-1827 is an orally active, selective agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In con ...

Varenicline Varenicline (trade name Chantix and Champix) is a medication used for smoking cessation. Varenicline is also used for the treatment of dry eye disease. The most common side-effects include nausea (feeling sick), insomnia (difficulty sleeping), a ...

Sazetidine A Sazetidine A (AMOP-H-OH) is a drug which acts as a subtype selective partial agonist at α4β2 neural nicotinic acetylcholine receptors, acting as an agonist at (α4)2(β2)3 pentamers, but as an antagonist at (α4)3(β2)2 pentamers. It has poten ...

: full agonist on (α4)₂(β2)₃, 6% efficacy on (α4)₃(β2)₂ *''N''-(3-pyridinyl)-bridged bicyclic diamines

PAMs

* NS-9283: 60-fold left-shifting of concentration-response curve, no change in maximum efficacy *

Desformylflustrabromine Desformylflustrabromine (dFBr) is a monomethyltryptamine derivative which was first isolated as a secondary metabolite of the marine bryozoan '' Flustra foliacea''. Bioactivity dFBr has been identified as a novel positive allosteric modula ...

* Further compounds.. (see references →)

Antagonists

* (−)-7-methyl-2-exo- '-(6-[18Fluoropyridin-2-yl)-5'-pyridinyl">8F.html" ;"title="'-(6-[18F">'-(6-[18Fluoropyridin-2-yl)-5'-pyridinyl7-azabicyclo[2.2.1]heptane * 2-fluoro-3-(4-nitro-phenyl)deschloroepibatidine * Coclaurine - alkaloid from ''Nelumbo nucifera'' * Mecamylamine *

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. Cono ...

* PNU-120,596 *

Bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the case ...

* Dihydro-β-erythroidine, selective *

Nitrous oxide Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has a ...

Isoflurane Isoflurane, sold under the brand name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia; however, other medications are often used to start anesthesia rather than isoflurane, due to airway irritation w ...

*1-(6-(((''R'',''S'')-7-Hydroxychroman-2-yl)methylamino]hexyl)-3-((''S'')-1-methylpyrrolidin-2-yl)pyridinium bromide (compound 2) ( Ligand (biochemistry)#Bivalent ligand, heterobivalent ligand: D2R agonist and

nAChR 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 ...

antagonist)

NAMs

* Oxantel

References

{{Nicotinic acetylcholine receptor modulators Ion channels Addiction Nicotinic acetylcholine receptors