PHA 568487

PHA 568487 a selective agonist of alpha-7 nicotinic acetylcholine receptor (α-7 nAchR)[1][2].PHA 568487 reduces neuroinflammation and oxidative stress[2]. PHA-568487 has rapid brain penetration[3].

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

Signaling Pathways >> Neuronal Signaling >> nAChR

Research Areas >> Inflammation/Immunology

Research Areas >> Neurological Disease

PHA 568487 increases anti-oxidant gene expression and decreases oxidative stress and phosphorylation of NF-κb p65. Methyllycaconitine (MLA) has the opposite effects[2]. PHA increases anti-oxidant genes and NADPH oxidase expression associated with decreased phosphorylation of NF-kB p65 in microglia/macrophages[3].

PHA 568487 attenuates neuronal injury and behavioral dysfunction in mice with ischemic stroke only and ischemic stroke plus tibia fracture[2]. PHA 568487 (1.25 mg/kg; i.p.; treated daily)-treated ischemic rats shows a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome[4]. Animal Model: C57BL/6J male mice (10-12 weeks old)[2] Dosage: PHA 568487 (PHA; 0.4 and 0.8 mg/kg); Methyllycaconitine (MLA; 4 and 6 mg/kg) Administration: Injected intraperitoneally once on day 1, or twice on days 1 and 2, after pMCAO Result: Injection of PHA (0.8 mg/kg) and MLA (6 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 (297 6±8.3 g)[4] Dosage: 1.25 mg/kg Administration: I.p.;0.1 mL; treated daily Result: Showed a significant reduction of the cerebral infarct volumes and an improvement of the neurologic outcome.

[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]. Dingquan Zou, et al.Activation of Alpha-7 Nicotinic Acetylcholine Receptor Reduces Brain Edema in Mice with Ischemic Stroke and Bone Fracture. Mol Neurobiol. 2017 Dec;54(10):8278-8286.

[4]. 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.