Nicotinic (α4β2) Receptors

Nicotinic α4β2 receptors have high affinity for nicotine and account for >90% of [3H]-nicotine binding to brain tissues. A stoichiometry of (α4)2(β2)3 has been proposed, generating two agonist binding sites consistent with the model of the muscle nAChR.

Products
Background
Literature
Gene Data

Agonists

Cat No Product Name / Activity
5017 A 85380 dihydrochloride
High affinity and selective α4β2 agonist
5079 ABT 089 dihydrochloride
High affinity and selective α4β2 partial agonist
3549 3-Bromocytisine
Potent agonist of α4β4, α4β2 and α7 nACh receptors
5236 CC4
High affinity and subtype-selective α6β2 and α4β2 partial agonist
5557 Dianicline
Selective α4β2 nAChR partial agonist
1518 5-Iodo-A-85380 dihydrochloride
High affinity α4β2 and α6β2 subtype-selective agonist
1527 5-Iodo-A-85380, 5-trimethylstannyl N-BOC derivative
Precursor to 5-Iodo-A-85380 (Cat. No. 1518)
3546 (-)-Nicotine ditartrate
Prototypical nAChR agonist
4125 3-pyr-Cytisine
High affinity, partial agonist of α4β2 receptors
1053 RJR 2403 oxalate
α4β2 selective nicotinic agonist
4766 SIB 1508Y maleate
Potent agonist of α4β2, α2β4, α4β4 and α3β4 nACh receptors
2737 TC 2559 difumarate
Selective partial agonist at α4β2 receptors
3754 Varenicline tartrate
Orally active, subtype-selective α4β2 partial agonist

Antagonists

Cat No Product Name / Activity
2349 Dihydro-β-erythroidine hydrobromide
Antagonist for neuronal α4-containing nicotinic receptors
2241 DMAB-anabaseine dihydrochloride
α4β2 nAChR antagonist; also partial agonist at α7 nAChR

Modulators

Cat No Product Name / Activity
5963 CMPI hydrochloride
Potent positive allosteric modulator of α4β2 nAChRs; also inhibitor of (α4)2(β2)3, muscle-type and Torpedo nAChRs
3328 Desformylflustrabromine hydrochloride
Positive allosteric modulator of α4β2; also muscle-type nAChR inhibitor
4141 LY 2087101
Potentiator of α4β2 nAChRs
5112 NS 9283
Positive allosteric modulator of α4β2

Other

Cat No Product Name / Activity
2736 Sazetidine A dihydrochloride
α4β2 receptor ligand; may act as an agonist or a desensitizer

Nicotinic α4β2 receptors have high affinity for nicotine and account for >90% of [3H]-nicotine binding to brain tissues. A stoichiometry of (α4)2(β2)3 has been proposed, generating two agonist binding sites consistent with the model of the muscle nAChR.

Manipulation of the stoichiometry of α4β2 nAChRs expressed in Xenopus oocytes indicates that (α4)3(β2)2 nAChRs are also viable, displaying lower affinity for ACh and higher Ca2+ permeability; whether native nAChRs with this subunit stoichiometry exist is not known.

Transgenic knockout of either of these subunits eliminates nicotine self administration, whereas virally targeted re-expression of the β2 subunit in mesolimbic areas of β2 knockout mice recovers this behavior, implicating a role for α4β2 nAChRs in nicotine addiction. α4β2 nAChRs are highly expressed in the thalamus and have been suggested to have a putative role in the thalamo-cortical circuitry. As a consequence of their putative role in thalamo-cortical circuitry, gain of function mutations in the M2 domain of either the α4 or β2 subunit give rise to some forms of autosomal dominant nocturnal frontal lobe epilepsy. The human genes encoding the nicotinic α4 and β2 receptor subunits have been localized to chromosomes 13 (q13.2-q13.3) and 1 (1q21.3) respectively.

External sources of pharmacological information for Nicotinic (α4β2) Receptors :

    Literature for Nicotinic (α4β2) Receptors

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    Nicotinic ACh Receptors Scientific Review

    Updated in 2014, this review by Sue Wonnacott summarizes the diverse structure and function of nicotinic acetylcholine receptors and gives an in-depth review of the ligands available for nAChR research. Compounds available from Tocris are listed.

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    Nicotinic (α4β2) Receptor Gene Data

    Gene Species Gene Symbol Gene Accession No. Protein Accession No.
    α4 Human CHRNA4 NM_000744 P43681
    Mouse Chrna4 NM_015730 O70174
    Rat Chrna4 NM_024354 P09483
    β2 Human CHRNB2 NM_000748 P17787
    Mouse Chrnb2 NM_009602 Q9ERK7
    Rat Chrnb2 NM_019297 P12390