The alpha-3 beta-4 nicotinic receptor, also known as the α3β4 receptor and the ganglion-type nicotinic receptor,Pharmacology, (Rang, Dale, Ritter & Moore, , 5th ed., Churchill Livingstone 2003) p. 138. is a type of

nicotinic acetylcholine receptor 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 ...

, consisting of α3 and β4

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, ...

s. It is located in the

autonomic ganglia An autonomic ganglion is a cluster of nerve cell bodies (a ganglion) in the autonomic nervous system. The two types are the sympathetic ganglion and the parasympathetic ganglion Parasympathetic ganglia are the autonomic ganglia of the parasympa ...

and

adrenal medulla The adrenal medulla ( la, medulla glandulae suprarenalis) is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of chromaffin cell ...

, where activation yields

post- ''Post-'' (stylized in all caps) is the third solo album by American singer-songwriter Jeff Rosenstock. It was released on January 1, 2018, without any promotional lead-up. The album was released on Polyvinyl Record Co. in the United States a ...

and/or presynaptic excitation, mainly by increased Na⁺ and K⁺ permeability. As with other nicotinic acetylcholine receptors, the α3β4 receptor is pentameric α3)_m(β4)_n where m + n = 5 The exact subunit

stoichiometry Stoichiometry refers to the relationship between the quantities of reactants and products before, during, and following chemical reactions. Stoichiometry is founded on the law of conservation of mass where the total mass of the reactants equ ...

is not known and it is possible that more than one functional α3β4 receptor assembles in vivo with varying subunit stoichiometries. Ligands which inhibit the α3β4 receptor have been shown to modulate drug-seeking behavior, making α3β4 a promising target for the development of novel antiaddictive agents.

Ligands

Agonists

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. Par ...

(

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

that binds non-selectively to nAChRs and

mAChRs Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

) *

Anabaseine Anabaseine (3,4,5,6-tetrahydro-2,3′-bipyridine) is an alkaloid toxin produced by '' Nemertines'' and ''Aphaenogaster'' ants. It is structurally similar to nicotine and anabasine. Similarly, it has been shown to act as an agonist on most nicotin ...

and other structural analogs *

Carbachol Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for var ...

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 cessa ...

(partial agonist) * Dimethylphenylpiperazinium *

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 ...

Lobeline Lobeline is a pyridine 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''), '' Lobelia c ...

Page 149 *

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

RJR-2429 RJR-2429 is a drug that acts as an agonist at neural nicotinic acetylcholine receptors, binding to both the α3β4 and the α4β2 subtypes. RJR-2429 is stronger than nicotine but weaker than epibatidine Epibatidine is a chlorinated alkaloid ...

Antagonists

Competitive

Zaveri's nAChR-selective ligand number 5 (2010) with tube model

* DHβE * SR 16584, highly selective over α4β2 and α7

Noncompetitive

Dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with b ...

Dextrorphan Dextrorphan (DXO) is a psychoactive drug of the morphinan class which acts as an antitussive or cough suppressant and dissociative hallucinogen. It is the dextrorotatory enantiomer of racemorphan; the levorotatory enantiomer is levorphanol. D ...

Dextropropoxyphene Dextropropoxyphene is an analgesic in the opioid category, patented in 1955 and manufactured by Eli Lilly and Company. It is an optical isomer of levopropoxyphene. It is intended to treat mild pain and also has antitussive (cough suppressant) ...

Hexamethonium Hexamethonium is a non-depolarising ganglionic blocker, a nicotinic (nAChR) receptor antagonist that acts in autonomic ganglia by binding mostly in or on the nAChR receptor, and not the acetylcholine binding site itself. It does not have any ef ...

* Imipramine *

Levacetylmethadol Levacetylmethadol (INN), levomethadyl acetate (USAN), OrLAAM (trade name) or levo-α-acetylmethadol (LAAM) is a synthetic opioid similar in structure to methadone. It has a long duration of action due to its active metabolites. Medical uses LAA ...

Mecamylamine Mecamylamine ( INN, BAN; or mecamylamine hydrochloride (USAN); brand names Inversine, Vecamyl) is a non-selective, non-competitive antagonist of the nicotinic acetylcholine receptors (nAChRs) that was introduced in the 1950s as an antihypertensi ...

Methadone Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroi ...

Tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or ...

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 cas ...

Reboxetine Reboxetine, sold under the brand name Edronax among others, is a drug of the norepinephrine reuptake inhibitor (NRI) class, marketed as an antidepressant by Pfizer for use in the treatment of major depression, although it has also been used of ...

Ibogaine Ibogaine is a naturally occurring psychoactive substance found in plants in the family Apocynaceae such as '' Tabernanthe iboga'', '' Voacanga africana'', and '' Tabernaemontana undulata''. It is a psychedelic with dissociative properties. Pre ...

Voacangine Voacangine (12-methoxyibogamine-18-carboxylic acid methyl ester) is an alkaloid found predominantly in the root bark of the '' Voacanga africana'' tree, as well as in other plants such as ''Tabernanthe iboga'', '' Tabernaemontana africana'', ''Tra ...

* 18-MC * 18-MAC * ME-18-MC * AT-1001 *

Choline Choline is an essential nutrient for humans and many other animals. Choline occurs as a cation that forms various salts (X− in the depicted formula is an undefined counteranion). Humans are capable of some ''de novo synthesis'' of choline but r ...

References