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 Thea7 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] ALICE L. BODNAR. Discovery and Structure−Activity Relationship of Quinuclidine Benzamides as Agonists of α7 Nicotinic Acetylcholine Receptors[J]. Journal of Medicinal Chemistry, 2005, 48 4: 905-908. DOI:10.1021/jm049363q
[2] VANESSA STUCKENHOLZ. The α7 nAChR agonist PNU-282987 reduces inflammation and MPTP-induced nigral dopaminergic cell loss in mice.[J]. Journal of Parkinson’s disease, 2013: 161-172. DOI:10.3233/jpd-120157
[3] PALOMA VICENS. Motor and anxiety effects of PNU-282987, an alpha7 nicotinic receptor agonist, and stress in an animal model of Alzheimer’s disease.[J]. Current Alzheimer research, 2013, 10 5: 516-523. DOI:10.2174/15672050113109990130
[4] ELISA NAVARRO . Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction[J]. Biochemical pharmacology, 2015, 97 4: Pages 473-481. DOI:10.1016/j.bcp.2015.07.022
[5] SAMANTHA L. MCLEAN . Nicotinic α7 and α4β2 agonists enhance the formation and retrieval of recognition memory: Potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders[J]. Behavioural Brain Research, 2016, 302: Pages 73-80. DOI:10.1016/j.bbr.2015.08.037