PF 04531083

PF 04531083 is an orally active and selective Na_V1.8 blocker with an IC₅₀ of 0.7 μM. PF 04531083 is a blood-brain barrier (BBB) penetrant compound. PF 04531083 can be used for the research of respiratory system and neuropathic/inflammatory pain^[1][2][3]. IC50 & Target:Na_V1.8^[1] In Vitro:PF 04531083 (1 μM) stimulates baseline activity by ~50% and the firing response to 10% CO₂ in chemosensitive retrotrapezoid nucleus (RTN) neuron in a slice from a Tcf4^tr/+ mice^[3].
PF 04531083 blocks human Na_v1.8, hNa_v1.1, hNa_v1.5, hNa_v1.7, TTX-r rat DRG, TTX-R hDRG, hERG with IC₅₀ values of 0.19, 37, 37, 36, 0.54, 0.2, >30 μM, respectively^[2].
In Vivo:PF 04531083 (1 mg/kg, i.v.; or 2 mg/kg, p.o.) is a low clearance compound with good bioavailability ∼60% in rats^[2].
PF 04531083 (40 mg/kg; 1.5 h) is efficacious in the tibial nerve transection (TNT) induced mechanical allodynia model in rat^[2].
PF 04531083 inhibits native tetrodotoxin-resistant (TTX-R) currents in rodent dorsal root ganglion (DRG) neurons with an IC₅₀ of 0.54 μM^[2].
PF 04531083 (40 mg/kg; 1.5 h) improves baseline breathing in Tcf4^tr/+ mice^[3].
PF 04531083 (30 min before test) improves behavioral abnormalities associated with Pitt-Hopkins syndrome (PTHS) in Tcf4^tr/+ mice^[3].