GSK-1482160

GSK-1482160 is an orally active and blood-brain barrier penetrant P2X7 receptor (P2X7R) negative allosteric modulator with pIC₅₀s of 8.5 (human) and 6.5 (rat). GSK-1482160 reduces the efficacy of ATP at the P2X7 receptor without affecting its affinity, thereby inhibiting the release of IL-1β. GSK-1482160 is an effective radioligand and can be labeled with radioactive isotopes like 11C or 18F to image P2X7R. GSK-1482160 can be used for the studies of chronic joint pain and chronic constriction injury (CCI)^[1][2][3]. In Vitro:GSK-1482160 (Compound 31) has extremely low clearance rates in both rat and human liver microsomes, and shows no significant inhibition on the major CYP450 subtypes (1A2, 2C9, 2C19, 2D6, 3A4)^[2].
In Vivo:GSK-1482160 (Compound 31) (5-50 mg/kg, p.o., twice daily for 5 days) effectively alleviates rats chronic inflammatory pain^[2].
GSK-1482160 (20 mg/kg, p.o., twice daily for 8 days) significantly reverses mechanical allodynia 1 h post dose on day 1 and this effect was maintained for the duration of the dosing period in the rat chronic constriction injury (CCI) model^[2].