Carbamates resistance mechanisms

Resistance mechanisms associated with changes in toxicokinetics are predominately cases of enhanced metabolic detoxication. With readily biodegradable insecticides such as pyrethroids and carbamates, enhanced detoxication by P450-based monooxygenase is a common resistance mechanism (see Table 4.3). 

The mechanism of carbamate-resistance, formerly considered to be enhanced hydrolysis (e.g. carbaryl to 1-naphthol), was found to derive almost exclusively from hydroxylation at various points on the molecule, not only the aromatic leaving group but also the N-methyl on the carbamate (Fig. 3), as well as some desmethylation for good measure (14). Pyrethrin-resistance, at first considered to be due to hydrolysis of the alcohol-acid linkage, was also found to be due to an oxidation, occurring at the transmethyl group of the isobutenyl side-chain of the chrysanthemic acid (15). 

Figure 3. Detoxicative mechanisms imparting carbamate-resistance (e.g. to carbaryl)...

Organophosphate resistance in M. persicae is due to the production of large amounts of carboxylesterase E4 that degrade as well as sequester these insecticides (12). This is believed to be the only biochemical resistance mechanism in this species in many countries, including the UK., continental Europe, Japan, and Australia (25.). E4 additionally confers low levels of resistance to carbamates and to (IS)-trans-permethrin (12). This esterase has been characterized extensively by toxicological, biochemical, immunological and molecular studies (2, 22, 22f 22, 22) ... 

Metabolic resistance mechanisms are still the most widely encountered causes for OP and carbamate resistance. Yet, after the first few cases of target site insensitivity were reported in the early 1970 s in mites and ticks, many such cases have been found also in insects. Resistance can also be enhanced by a decreased rate of penetration through the integument. This resistance mechanism by itself is of minor importance, but provides an increased opportunity for detoxification. A 50-fold increase in resistance to carbaryl was seen in a house fly strain, in which a gene for reduced penetration had been combined (by selective breeding) with a gene for increased detoxification (5). 

Reviews on detoxification. All the enzyme systems involved in carbamate and OP metabolism and detoxification have been described in detail by several recent reviewers (7. 43-45. For an in-depth discussion of the genetics of these resistance mechanisms, see Oppenoorth (28). 

The major difference between OPs and carbamates is in their metabolic fate. This strongly indicates that metabolism and detoxification are the most important factors in resistance evolution. The current emphasis on target site interactions and their associated resistance mechanisms reflects their perceived practical importance, the importance of their study for the development of new insecticidal molecules, and the fundability of such research. But detailed studies of the biochemical characteristics and physiological behavior of the enzymes involved in insecticide metabolism and detoxification are still very important. 

Recently, another important class of chemicals based on the oxadiazolone ring have shown activity similar to the carbamates, but with surprising activity on carbamate-resistant green rice leafhopper (Structure, Table 2) (11-13). To Investigate the resistance mechanism in green rice leafhopper, we decided to explore the structure-activity relations of both insecticide classes against AChE preparations from susceptible and resistant insects. The difference in the substituent effects was expected to provide critical information at the molecular level of the receptor complex. 

L.G. Davidse and W. Flach, Differential Binding of Benzimidazol-2-yl Carbamate to Fungal Tubulin as a Mechanism of Resistance to this Antimitotic Agent in Mutant Strains of Aspergillus nidulans J. Cell. Biol., 1977, 72, 174-193. 

Decreased uptake as a mechanism of resistance was also observed in houseflies resistant to organochlorine, organophosphate, and carbamate insecticides. Resistant strains had higher total lipids, monoglycerides, diglycerides, fatty acids, sterols, and phospholipids in the cuticle than did the susceptible strain (Patil and Guthrie, 1979). 

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