Mode of action studies with formetanate and formparanate acaricides

Formetanate and formparanate acaricides are very toxic to rats, houseflies (Musca domestica L.), and two-spotted spider mites (Tetranychus urticae Koch). Both compounds inhibit acetylcholine deacetylation by acetylcholinesterase (AChE) from the three organisms in vitro, and AChE activity in vivo was also depressed in rats, house-flies, and two-spotted spider mites poisoned with formetanate. Moreover, an excellent correlation was obtained between toxicity and in vivo AChE inhibition in formetanate-poisoned animals, and analyses of rat brains, housefly heads, and whole spider mites at various posttreatment intervals revealed that the concentration of formetanate-14C equivalents was generally related directly to the degree of AChE inhibition. Therefore, it is concluded that blockage of AChE by formetanate is the fundamental biochemical lesion and is responsible for initiation of the sequence of events that eventually lead to death of the rat, housefly, and two-spotted spider mite.