PHA 568487 a selective agonist of alpha-7 nicotinic acetylcholine receptor ( α-7 nAchR ). PHA-568487 shows rapid brain penetration. PHA 568487 reduces oxidative stress and neuroinflammation.

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.