This is largely because existing sodium-channel-blocking drugs recognize regions that are common to all members of the VGSC family and, as such, are not specific.
How can individual members of the VGSC family be controlled in just the preferred tissue?
Identification and profiling of individual members of the VGSC family, particularly those with nociceptors as their primary residence, has opened up the exciting possibility of therapies aimed specifically at hyperexcitable nociceptors, precluding any off-target side effects.
Discoveries of molecules that assist VGSCs in nociceptor hyperexcitability are enlarging the ensemble of potential targets that can be tested (Sharkey et al.
Our demonstration of the ability of permethrin to antagonize deltamethrin-induced VGSC activation indicates that permethrin also interacts with VGSCs in cerebrocortical neurons.
Studies of binary combinations of pyrethroids indicate that type I and type II compounds may act competitively on VGSCs (Motomura and Narahashi 2001; Song et al.
A comprehensive study of the relative potencies of pyrethroids on VGSCs in intact mammalian neurons has not previously been undertaken.
To confirm the role of VGSCs in pyrethroid-induced increases of [Na.
influx; thus, we sought to confirm that they interacted with VGSCs in mouse neurons.
VGSCs are well-established targets of pyrethroid effects and clearly contribute to the insecticidal and toxicological actions of these compounds (Narahashi 1996).
Pyrethroid compounds are chiral and their stereoisomers have differing activities toward VGSCs (Lund and Narahashi 1982).