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

Nav1.8 channel:196 nM

PF-01247324抑制人类背根神经节(DRG)神经元中的天然耐受河豚毒素(TTX-R)电流(IC50：331 nM)及重组表达的h Nav1.8通道(IC50：196 nM)，对重组表达的TTX-R hNav1.5通道具有50倍选择性(IC50：10 μM)，对TTX敏感(TTX-S)通道具有65-100倍选择性(IC50：10-18 μM)。体外电流钳测试显示，PF-01247324降低了大鼠和人类DRG神经元的兴奋性，并改变了动作电位的波形[1]。

PF-01247324 (100 mg/kg) 通过减少第二阶段的抽动37%显示出其效果。在大鼠模型的卡拉胶诱导的热痛觉过敏和CFA诱导的机械痛觉过敏实验中，30 mg/kg的PF-01247324分别在0.218和0.126 μM的浓度下表现出显著效果[1]。相较于对照组，接受PF-01247324处理的小鼠在运动协调性和类小脑症状方面有明显改善[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].