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Description: PF-01247324 is a novel, potent, selective and orally bioavailable Nav1.8 channel blocker with an IC50 of 196 nM for recombinant human Nav1.8 channel. PF-01247324 was administered by oral gavage at 1000 mg/kg; control groups received an equal volume of vehicle. Behavioral assays of motor coordination, grip strength, and ataxia were performed. We observed significant improvements in motor coordination and cerebellar-like symptoms in mice that received PF-01247324 compared to control littermates that received vehicle. These preclinical proof-of-concept data suggest that PF-01247324, its derivatives, or other Nav1.8-selective blockers merit further study for providing symptomatic therapy for cerebellar dysfunction in MS and related disorders. NaV 1.8 ion channels have been highlighted as important molecular targets for the design of low MW blockers for the treatment of chronic pain.
References: Br J Pharmacol. 2015 May; 172(10):2654-70.; PLoS One. 2015 Mar 6; 10(3):e0119067.
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