A 582941

A 582941 has been shown to provide glycogen synthase kinase-3β activation and α7 nicotinic receptors in Aβ1-42-induced tau phosphorylation in PC12 cells, which is useful in neurodegeneration associated with Alzheimer''s disease research.

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].

α7 nAChR: 10.8 nM (Ki, for rat α7 receptors); α7 nAChR: 16.7 nM (Ki, for human α7 receptors); 5-HT₃ Receptor: 150 nM (Ki)

Desiccate at RT

[1]. tietje kr, anderson dj, bitner rs, et al. preclinical characterization of a-582941: a novel α7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties. cns neuroscience & therapeutics, 2008, 14(1): 65-82.