Oral administration of PF-01247324 partially reverses motor incoordination in transgenic mice overexpressing Nav1.8 in cerebellar Purkinje neurons.

<p><b>A</b>. Latency to fall from an inverted wire grid was measured in L7–1.8TG mice administered either PF-01247324 or vehicle, and in their wildtype littermates. Behavioral testing was performed one hour after dosing. Differences between the three groups were significant (one-way ANOVA, p = 0.0014). L7–1.8TG mice in the vehicle group performed significantly worse than WT mice. L7–1.8TG mice that received oral dosing of PF-01247324 had significantly improved performance in this assay. <b>B</b>. In the rotarod test, significant differences in motor coordination were observed (one-way ANOVA, p = 0.0006). L7–1.8TG mice in the vehicle group were able to stay on the rotating beam for less time than WT mice, indicating a deficit in motor coordination. Oral administration of PF-01247324 to L7–1.8TG mice significantly improved their performance compared to vehicle-treated mice of the same genotype. <b>C</b>. Grip strength was similar in each of the three groups. One-way ANOVA, p = 0.7560. *, p<0.05 compared to WT vehicle group; #, p<0.05 compared to L7–1.8TG vehicle group, Dunnett’s post-hoc test. WT+vehicle, n = 8; L7–1.8TG+vehicle, n = 7; L7–1.8TG+PF-01247324, n = 6.