Effects of synergists on the metabolism and toxicity of anticholinesterases.

Insecticide synergists enhance insecticidal action through their ability to block the enzymatic detoxification of insecticides with which they are combined. The structure of the synergist is therefore determined by the nature of the insecticide and the critical biochemical pathway responsible for its degradation.Synergists can be broadly classified as either analogue synergists, whose structure closely resembles that of the insecticide they synergize, or inhibitors of microsomal oxidation. Metabolism of the phenyl methylcarbamates is effected largely by the microsomal enzymes. Consequently microsomal enzyme inhibitors, such as the methylenedioxyphenyl compounds, the aryloxyalkylamines, the thiocyanates, the propynyl aryl ethers, and the 1,2,3-benzothiadiazoles, are all effective carbamate synergists. The detoxification pathways of the organophosphates, however, are more complex and include hydrolysis, dealkylation, and carboxylesterase pathways as well as oxidation. Because phosphorothioates are activated by oxidation, their toxicity is often antagonized by oxidase inhibitors. The effectiveness of different synergists towards resistant strains of insects is likely to vary in a manner that reflects the critical metabolic pathway on which resistance depends.