Inhibitors pyrethroid potentiation

Fenvalerate has low toxicity in mammals due to its rapid metabolic breakdown. It acts directly on nerve axons by prolonging sodium channel opening in cell membranes. Insects exposed to fenvalerate are quickly paralyzed exposure causes quick insect knockdown. In small animals, type II pyrethroids cause salivation, chewing, burrowing, choreoathetosis, and seizures. They also cause lower action potential amplitude, marked membrane depolarization, and eventual total neural activity blockade. Fenvalerate is likely to act both on peripheral and central nervous system. It is also a potent inhibitor of calcineurin (protein phosphatase 2B). 

Janecki, T., A convenient synthesis of substituted 2-cyano-l,3-butadienes, Synthesis. 167, 1991. Ting, P.C., and Solomon, D.M., Synthesis of spiro[4, 5, 10,11-tetrahydro-5//-dibenzo[a,d]cyclohep-ten-5-yl-2 (37/)-furans] as potential cytokine inhibitors, J. Heterocycl. Chem., 32, 1027, 1995. Armesto, D., flail ego, M.G., Horspool, W.M., and Agarrabeitia, A.R., A new photochemical synthesis of cyclopropanecarboxylic acids present in pyrethroids by the aza-di-Jt-methane reanangement. Tetrahedron, 51, 9223, 1995. 

Since OPs inhibit serine hydrolases such as AChE by phosphorylating them, it follows that OPs are potential inhibitors of all other serine hydrolases. This means that OPs can be used as synergists, notably for the pyrethroids that are detoxified by ester hydrolysis, and OP-containing mixture have proven successful in several cases (34.) The usefulness of these mixtures can be prolonged by using them in rotations with other mixtures and/or insecticides. 

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