Target sites for insecticides

However, cockroaches dosed with AOB ethyl ester in vivo showed 70-80% inhibition of flight muscle GAD, irrespective of symptoms. This suggests that GAD may not be a very promising target site for insecticides either. 

The original purpose of this study was to address the issue of whether GABA-T was a realistic target site for insecticides. A range of inhibitors was synthesized and tested in vitro and in vivo. One interesting finding from the in vitro experiments was that aminooxybutyrate was over 50 times more potent than aminooxyacetate, which is a "standard" inhibitor in the literature (12). The data... 

The sodium channel in the nerve membrane is the major target site for all synthetic pyrethroid insecticides (and many other neurotoxicants)... 

This is a target site for very few current insecticides, and resistance to compounds acting there has not been developed. This discovery gave additional momentum to the synthesis program. Eventually compounds with activity comparable to the synthetic pyrethroids were discovered (50) and investigations in this area continue. 

Complex III has been very successfully exploited as a target site for fungicides such as the strobilurins, fanoxadone and fenamidone [75]. However, it has only been in the last few years that insecticidal or acaricidal products have used inhibition at Complex III as a mode of action. 

Federici, B.A. 1993. Insecticidal bacterial proteins identify the midgut epithelium as a source of novel target sites for insect control. Arch. Insect Biochem. Physiol. 22 357-371. 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

Although structurally-diverse as evidenced above, the insecticidal pyrethroids still conform to a unique, operationally-defined, structure-activity relationship based on the physical characteristics and three-dimensional shape of the entire molecule conforming to those originally evidenced in the natural pyrethrins [13]. From this relationship, it becomes apparent that there is no single molecular aspect or reactive moiety that serves as a true toxophore for the pyrethroids and that their actions at target sites are dependent upon the entire stereospecific structure of these insecticides [1]. 

The establishment of a common mechanism of mammalian toxicity for the pyrethroids is not a straight forward process, as it was for the organophosphorus and carbamate insecticides, due to the occurrence of multiple potential target sites and the varied action of pyrethroids at these sites as reviewed above. In view of... 

Work in our laboratory on various parameters in R and S fish has investigated the factor(s) responsible for resistance. The results have indicated that resistance is multifactorial, involving a barrier to insecticide penetration, insecticide storage, insecticide metabolism, and an apparent "insensitivity" at the target site to the toxic effects of the insecticide. The present report concentrates on two of these factors insecticide disposition and metabolism. 

Hepatic mixed-function oxidase activities demonstrated seasonal trends, with higher specific activities in the cold weather months in both populations with few differences in enzyme activities or cytochrome levels between the two populations. Metabolism of aldrin, dieldrin and DDT was similar between the two populations. R fish have larger relative liver size and, therefore, a greater potential for xenobiotic metabolism. However, biotransformation appears to be of minor importance in chlorinated alicyclic insecticide resistance in mosquitofish barriers to penetration appear to be of greater importance and an implied target site insensitivity appears to be the most important factor in resistance. 

Oberlander, H. and Smagghe, G., Imaginal discs and tissue cultures as targets for insecticide action, in Biochemical sites of insecticide action and resistance, Ishaaya, I., Ed., Berlin Springer, 2001, p. 133. 

Yu and Nguyen (1996) showed that selection of a strain of diamondback moth (Plu-tella xylostella) with permethrin for 21 generations resulted in over 600-fold resistance to permethrin in this strain. The resistant strain was also cross-resistant to all pyrethroids tested, including bifenthrin, fenvalerate, esfenvalerate, A.-cyhalothrin, fluvalinate, and tral-omethrin. However, it remained susceptible to organophosphate, carbamate, cyclodiene, neonicotinoid, avermectin, and microbial insecticides tested. Biochemical studies indicated that pyrethroid resistance observed in this strain was most likely due to decreased target site sensitivity. 

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