PNU 282987

PNU-282987 is a selective α7 nicotinic acetylcholine receptor(α7 nAChR) agonist with Ki of 26 nM; no affinity for α1β1γδ and α3β4 nAChRs (IC50 ≥ 60 μM).IC50 value: 26 nM(Ki) [1]Target: α7 nAChR agonistin vitro: Treatment with PNU-282987 resulted in an attenuation of neuroinflammation in the MPTP-lesioned SN. Furthermore, PNU-282987 attenuated MPTP-induced dopaminergic cell loss in the SN and reduced striatal dopamine depletion [3].in vivo: Mice were subjected to 70% partial hepatic I/R for 60 min and pretreated with either vehicle or with PNU-282987, and blood and hepatic tissue samples were collected at 3, 6, and 12 h following reperfusion. pretreatment with PNU-282987 decreased serum transaminase levels and ameliorated liver injury after hepatic I/R. Moreover, pretreatment with PNU-282987 suppressed NF-κB activation, cytokine production (tumor necrosis factor α, interleukin 1β), and HMGB1 expression in liver after hepatic I/R [2]. Mice treated with 2.5 and 10 mg/kg of PNU devoted less time to rearing into open arms. In the HB task, MC mice displayed higher exploratory activity reflected in more head-dips (HD) during the first minute than EE and SE, whereas EE displayed low exploration levels reflected in total HD (5 min) [4].

References:
[1]. Bodnar AL, et al. Discovery and structure-activity relationship of quinuclidine benzamides as agonists of alpha7 nicotinic acetylcholine receptors. J Med Chem. 2005 Feb 24;48(4):905-8.
[2]. Dong Jun Yu, et al. Effect of ischemic preconditioning combined with α7 nAchR agonists on limb ischemia-reperfusion lung injury in rat. Biomed Res. 2017; Special Issue: ISSN 0970.
[3]. Li F, et al. The protective effect of PNU-282987, a selective α7 nicotinic acetylcholine receptor agonist, on the hepatic ischemia-reperfusion injury is associated with the inhibition of high-mobility group box 1 protein expression and nuclear factor κB activation in mice. Shock. 2013 Feb;39(2):197-203.
[4]. Stuckenholz V, et al. The α7 nAChR agonist PNU-282987 reduces inflammation and MPTP-induced nigral dopaminergic cell loss in mice. J Parkinsons Dis. 2013;3(2):161-72.
[5]. Mesa-Gresa P, et al. Behavioral effects of different enriched environments in mice treated with the cholinergic agonist PNU-282987. Behav Processes. 2014 Mar;103:117-24.