PF-06526290 can both enhance and inhibit conduction through voltage-gated sodium channels.

Background And Purpose: Pharmacological agents that either inhibit or enhance flux of ions through voltage-gated sodium (Na ) channels may provide opportunities for treatment of human health disorders. During studies to characterize agents that modulate Na 1.3 function, we identified a compound that appears to exhibit both enhancement and inhibition of sodium ion conduction that appeared to be dependent on the gating state that the channel was in.

Addition of a single methyl group to a small molecule sodium channel inhibitor introduces a new mode of gating modulation.

Background And Purpose: Aryl sulfonamide Nav 1.3 or Nav 1.7 voltage-gated sodium (Nav ) channel inhibitors interact with the Domain 4 voltage sensor domain (D4 VSD).

A novel selective and orally bioavailable Nav 1.8 channel blocker, PF-01247324, attenuates nociception and sensory neuron excitability.

Background And Purpose: 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. Here, we describe the effects of PF-01247324, a new generation, selective, orally bioavailable Nav 1.