Thealpha-7 nicotinic receptor, also known as theα7 receptor, is a type ofnicotinic acetylcholine receptor implicated in long-term memory, consisting entirely ofα7subunits.[1] As with other nicotinic acetylcholine receptors, functional α7 receptors arepentameric [i.e., (α7)5stoichiometry].
Further, recent work has implicated this receptor as being important for generation of adult mammal neurons in the retina.[2] Functional α7 receptors are present in thesubmucous plexus neurons of the guinea-pigileum.[3]
The α7 receptor is highly implicated in the efficacy ofVarenicline for smoking cessation therapy significantly more thanα4β2 which is responsible for Nicotine's rewarding effects.Upregulation of α7-nAChR's is greatly correlated with a stronger response.[7]
An α7 nicotinic agonist appears to have positive effects on neurocognition in persons withschizophrenia.[8]
Activation of α7 nicotinic acetylcholine receptor on mast cells, is a mechanism by which nicotine enhances atherosclerosis.[9]
NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant[32]
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[33] In clinical development for cognitive deficits in schizophrenia.
It is found thatanandamide and ethanol cause an additive inhibition on the function of α7-receptor by interacting with distinct regions of the receptor. Althoughethanol inhibition of the α7-receptor is likely to involve theN-terminal region of the receptor, the site of action for anandamide is located in thetransmembrane andcarboxyl-terminal domains of the receptors.[39]
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^Mazurov A, Klucik J, Miao L, Phillips TY, Seamans A, Schmitt JD, Hauser TA, Johnson RT, Miller C (April 2005). "2-(Arylmethyl)-3-substituted quinuclidines as selective alpha 7 nicotinic receptor ligands".Bioorganic & Medicinal Chemistry Letters.15 (8):2073–7.doi:10.1016/j.bmcl.2005.02.045.PMID15808471.
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^Preskorn SH, Gawryl M, Dgetluck N, Palfreyman M, Bauer LO, Hilt DC (January 2014). "Normalizing effects of EVP-6124, an α-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia".Journal of Psychiatric Practice.20 (1):12–24.doi:10.1097/01.pra.0000442935.15833.c5.PMID24419307.S2CID19669958.
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^Walker DP, Wishka DG, Piotrowski DW, Jia S, Reitz SC, Yates KM, et al. (December 2006). "Design, synthesis, structure-activity relationship, and in vivo activity of azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists".Bioorganic & Medicinal Chemistry.14 (24):8219–48.doi:10.1016/j.bmc.2006.09.019.PMID17011782.
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