PF-01247324 is a selective and orally bioavailable Nav1.8 channel blocker [IC50: 196 nM].

Nav1.8 channel:196 nM

PF-01247324 inhibits native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50: 331 nM) and recombinantly expressed h Nav1.8 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 demonstrates that PF-01247324 reduces excitability in both rat and human DRG neurons and alters the action potential waveform [1].

PF-01247324 (100 mg/kg) reduces phase 2 flinching by 37%. 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].

Rats: . For male Sprague Dawley rats (170-300?g), PF-01247324 is formulated as solutions of 0, 10, 30, 100?mg/kg in 0.5%MC/0.1%Tween 80 vehicle and dosed via oral gavage prior to behavioral testing. Test animals are placed in a box separated by walls with a wire mesh floor allowing access to the plantar surface of the paw. Tactile testing is conducted[1]. Mice: . PF-01247324 is suspended in 0.5% methylcellulose, 0.1% Tween 80 and administered by oral gavage at a dose of 1000 mg/kg in a volume of 10 mL/kg one hour before behavioral testing. Control groups are administered an equal volume of the vehicle[2].