Permethrin (NRDC-143)

Permethrin is a modulator of voltage-gated sodium channels (Na_V) that is used as an insecticide.¹ It delays channel deactivation of the Na_V1.8 channel expressed in X. laevis oocytes. It is at least 100-fold more potent at insect than mammalian sodium channels, leading to slow deactivation of D. para/TipE, but not rat brain IIA or β1, sodium channels expressed in X. laevis oocytes when used at a concentration of 500 nM.² Permethrin (5 ?M) increases sodium influx in BV-2 and primary microglial cells by approximately 28 and 29%, respectively, and activates microglia.³ Long-term application of permethrin leads to dose- and time-dependent intracellular sodium accumulation and TNF-α release in microglia in vitro. Formulations containing permethrin have been used for the treatment of head lice and scabies infestations.

1.Choi, J.S., and Soderlund, D.M.Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytesToxicol. Appl. Pharmacol.211(3)233-244(2006) 2.Warmke, J.W., Reenan, R.A., Wang, P., et al.Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacologyJ. Gen. Physiol.110(2)119-133(1997) 3.Hossain, M.M., Liu, J., and Richardson, J.R.Pyrethroid insecticides directly activate microglia through interaction with voltage-gated sodium channelsToxicol. Sci.155(1)112-123(2017)