We have proposed that since the type II
pyrethroids deltamethrin and
cypermethrin, but not the type I
pyrethroid cismethrin act on
chloride channels, this could contribute to the bimodal nature of
pyrethroid poisoning syndromes. We now examine a wider range of
pyrethroid structures on the activity of these
calcium-independent voltage-gated maxi-
chloride channels. Excised inside-out membrane patches from differentiated mouse
neuroblastoma cells were used, and mean channel open probabilities calculated. For single dosing
at 10 microM,
bioallethrin,
beta-cyfluthrin,
cypermethrin,
deltamethrin, and
fenpropathrin were all found to significantly decrease open channel probability (p < 0.05).
Bifenthrin,
bioresmethrin, cispermethrin, cisresmethrin,
cyfluthrin isomers 2 and 4,
lambda-cyhalothrin,
esfenvalerate, and
tefluthrin, did not significantly alter open channel probability (p > 0.05). Since the type II
pyrethroids,
esfenvalerate, and
lambda-cyhalothrin were ineffective, we must conclude that actions at the
chloride ion channel target cannot in themselves account for the differences between the two types of
poisoning syndrome. Sequential dosing with type II
pyrethroids caused no further
chloride ion channel closure. The type I
pyrethroid cisresmethrin did however prevent a subsequent effect by the mixed type
pyrethroid fenpropathrin. In contrast, the type I
pyrethroid cispermethrin did not prevent a subsequent effect due to the type II
pyrethroid deltamethrin. The difference in effect may be the result of differences in potency, as
deltamethrin had a greater effect than
fenpropathrin. It therefore appears clear that in some combinations the type I and type II
pyrethroids can compete and may bind to the same
chloride channel target site.