N-(3R)-1-AZABICYCLO[2.2.2]OCT-3-YL-4-CHLOROBENZAMIDE

Description

PNU 282987 (CAS 123464-89-1) is a selective α7 nicotinic acetylcholine receptor (nAChR) agonist (Ki?= 26 nM).1? The?a7 nAChR is a potential therapeutic target of cognitive deficits in diseases such as Alzheimer’s, Parkinson’s, schizophrenia, and attention deficit disorders – agonism of this receptor with PNU 282987 has shown potential to ameliorate these deficits.2-5

Uses

PNU 282987 is used as an activator of α-7 nicotinic acetylcholine receptor.

General Description

A potent agonist highly selective for α7 nAChRs (K_i = 26 nM). Used in investigating the roles of α7 nAChRs in sensory gating, learning and memory, cognitive functions, and treatment of Schizophrenia.

Biological Activity

Highly selective α 7 nAChR agonist (K i = 26 nM) displaying negligible blockade of α 1 β 1 γ δ and α 3 β 4 nAChRs (IC 50 ≥ 60 μ M). Found to be inactive against a panel of 32 receptors at 1 μ M, except 5-HT 3 receptors (K i = 930 nM).

Biochem/physiol Actions

Primary Targetα7 nAChRs

References

1) Bodnar?et al.?(2005),?Discovery and structure-activity relationship of quinuclidine benzamides as agonists of α7 nicotinic acetylcholine receptors; J. Med. Chem.?48?905 2) Stuckenholz?et al.?(2013),?The α7 nAChR agonist PNU-282987 reduces inflammation and MPTP-induced nigral dopaminergic cell loss in mice; J. Parkinsons Dis.?3?161 3) Vicens?et al. (2013),?Motor and anxiety effects of PNU-282987, an alpha7 nicotinic receptor agonist, and stress in an animal model of Alzheimer’s disease; Curr. Alzheimer Res.?10?516 4) Navarro?et al.?(2015),?Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction; Biochem. Pharmacol.?97?473 5) McLean?et al.?(2016),?Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders; Behav. Brain Res.?302?73