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Overview
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Background
A 582941 is a highly selective partial agonist of α7 nicotinic acetylcholine receptors (nAChRs), with an EC50 value of 4260 nM to human α7 nAChRs [1].nAChRs are a family of pentameric ligand-gated ion channels. They are derived from multiple α (α2-α10) and β (β2-β4) subunit genes. α7 nAChR receptor exhibits higher Ca2+ permeability than other nAChR combinations. These receptors modulate the release of multiple neurotransmitters, including acetylcholine (ACh), glutamate, and GABA [1].In FLIPR, A 582941 did not activate recombinant heteromeric nAChRs (α4β2, α3β2, α3β4, or α4β4) according to Ca2+ dynamics results. In IMR-32 cells expressing native human α3β4 nAChRs, A 582941 did not produce an agonist effect (with an efficacy less than 20% at concentrations up to 100,000 nM). In Xenopus oocytes expressing an α9α10 nAChR construct, A 582941 at concentrations up to 100,000 nM did not evoke currents. With respect to nAChRs, A 582941 activated only the homomeric α7 subtype [1]. In a rat model of short-term memory based on olfactory cues, saline-treated adults used investigation times during the second session nearly equal to the first session, exhibiting little recognition of the juvenile. Treatment with A 582941 in adult rats resulted in a dose-related reduction in the exploration time during the second session compared with the first session, exhibiting improved recognition of the juvenile [1].
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