PF-01247324

PF-01247324 is a selective and orally bioavailable Na_v1.8 channel blocker with an IC₅₀ of 196 nM for recombinant human Na_v1.8 channel. IC50 & Target: IC50: 196 nM (hNa_v1.8)^[1] In Vitro: PF-01247324 inhibits native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC₅₀=331 nM) and in recombinantly expressed h Na_v1.8 channels (IC₅₀=196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav1.5 channels (IC₅₀=10 μM) and 65-100-fold selectivity over TTX-sensitive (TTX-S) channels (IC₅₀=10-18 μM). In vitro current clamp shows that PF-01247324 reduces excitability in both rat and human DRG neurons and also alters the waveform of the action potential^[1]. In Vivo: Experiments n rodents demonstrates efficacy in both inflammatory and neuropathic pain models. PF-01247324 reduces phase 2 flinching by 37% at 100 mg/kg. There is a significant effect of 30 mg/kg of PF-01247324 in the rat model carrageenan-induced thermal hyperalgesia and in CFA-induced mechanical hyperalgesia at exposures of 0.218 and 0.126 μM respectively^[1]. Mice that received PF-01247324 shows significant improvements in motor coordination and cerebellar-like symptoms compared to control^[2].