PHA 568487

PHA 568487 free base is a selective alpha 7 nicotinic acetylcholine receptor (α-7 nAchR) agonist. PHA 568487 free base reduces neuroinflammation[1][2][3].

Signaling Pathways >> Membrane Transporter/Ion Channel >> nAChR

Signaling Pathways >> Neuronal Signaling >> nAChR

Research Areas >> Neurological Disease

PHA 568487, α-7 nAchR-specific agonist, prevents NF-κb activation in the cells[2]. PHA 568487 treatment significantly reduces the expression of leukocyte infiltration molecules in MCAO rats and in endothelial cells after in vitro ischemia[3].

PHA 568487 treatment reduces mouse cognitive decline caused by aseptic bone fracture by promoting inflammation resolution. PHA 568487 (PHA; 0.8 mg/kg; injected intraperitoneally) reduces infarct volume and TUNEL positive neurons in the peri-infarct regions of permanent middle cerebral artery occlusion (pMCAO) and pMCAO+tibia fracture mice[2]. The role played by a7 receptors on neuroinflammation is supported by the decrease of [18F]DPA-714 binding in ischemic rats treated with the a7 agonist PHA 568487 at day 7 after MCAO[3]. PHA 568487-treated ischemic rats show a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome compared with non-treated MCAO rats[3]. Animal Model: C57BL/6J male mice (10-12 weeks old) with pMCAO[2] Dosage: 0.4 and 0.8 mg/kg Administration: Injected intraperitoneally once on day 1, or twice on days 1 and 2, after pMCAO Result: 0.8 mg/kg on days 1 and 2 after pMCAO yielded the best effect on infarct volume and behavior tests. Animal Model: Adult male Sprague-Dawley rats[3] Dosage: 1.25 mg/kg Administration: Treated i.p. daily with 0.1 mL Result: Showed a significant decrease of [18F]DPA-714 binding in the ischemic cerebral hemisphere in comparison to non-treated ischemic rats.

[1]. F Barclay Shilliday, et al. Multiple species metabolism of PHA-568487, a selective alpha 7 nicotinic acetylcholine receptor agonist. Drug Metab Lett. 2010 Aug;4(3):162-72.

[2]. Zhenying Han, et al. Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture. J Neurochem. 2014 Nov;131(4):498-508.

[3]. Lorena Colás, et al. In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia. Glia. 2018 Aug;66(8):1611-1624.