Potentiation pyrethroid insecticides

Ion transport is central to nerve impulse transmission both along the axon and at the synapse and many neurotoxicants elicit effects by interfering with the normal transport of these ions (Figure 11.6). The action potential of an axon is maintained by the high concentration of sodium on the outside of the cell as compared to the low concentration inside. Active transporters of sodium (Na+K+ ATPases) that actively transport sodium out of the cell establish this action potential. One action of the insecticide DDT resulting in its acute toxicity is the inhibition of these Na+K+ ATPases resulting in the inability of the nerve to establish an action potential. Pyrethroid insecticides also elicit neurotoxicity through this mechanism. DDT also inhibits Ca2+Mg2+ ATPases, which are important to neuronal repolarization and the cessation of impulse transmission across synapses. 

Multifluorinated aromatics also play a significant role within bioactive compounds. Difluoroaromatics have already been discussed in Chapter 3. Bioactive tetrafluorobenzene derivatives are exemplified by the pyrethroid insecticides transfluthrin (6-9) and tefluthrin (6-10), whereas there are numerous pentafluorobenzene compounds that have proved of interest as potential insecticides, anticancer or antiglaucoma drugs (6-11,6-12, and 6-13) (Fig. 6.5). 

Decreased renal excretion of penicillin when coadministered with probenecid, potentiating its therapeutic effect Ops (profenofos, sulprofos, DEF) potentiate the toxicity of fenvalerate and malathion by inhibiting esterase, which detoxifies many pyrethroid insecticides and malathion... 

PRO (Fig. 9.1) is an economically important, widely used synergist of natural pyrethrins and synthetic pyrethroid insecticides with ait excellent record of human health anti safety over the 40 years or so since its introduction. Most pynelhnoids have a good record of environmental and human safety in the absence of PBO. a much greater tonnage of more potent, synthetic insecticides would be required to achieve the same levels of insect control, with potential adverse consequences for the natural environment. 

Houseflies on Danish farms have become resistant to almost every new insecticide introduced for their control since the 1950 s (M.). In the mid 1970 s, scientists showed that resistance to DDT and the new pyrethroid insecticides is due to a common resistance factor (the kdr and super-kdr genes), and they predicted that rapid resistance development to the more persistent SP compounds would rapidly evolve in the field. In 1978-79, surveys for SP resistance indicated that resistance to long-residual compounds was beginning to develop in the field. Overall, the survey data indicated that resistance would soon be widespread. Several steps were immediately taken to evaluate the resistance potential of... 

Spencer, C.I. et al.. Actions of pyrethroid insecticides on sodium currents, action potentials, and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts. J. Pharmacol. Exp. Therap. 298, 1067, 2001. 

Pyrethrin and pyrethroid insecticides are effective against a variety of insect pests on companion animals and livestock, and are used on farms, in the home, and garden and have many public health implications because of the safety associated with these compounds. The great potential of pyrethroids for the control of ffies, tsetse flies, fleas, and ticks is known. 

Hutson DH, Logan CJ (1986) The metabolic fate in rats of the pyrethroid insecticide WL85871,a mixture of two isomers of cypmnethrin. Pestic Sci 17 548-558 lARC (1991) Occupational exposures in insecticide application and some pesticides. lARC, Lyon Inoue S, Howgate EM, Rowland-Yeo K, Shimada T, Yamazaki H, Tucker GT, Rostami-Hodjegan A (2006) Prediction of in vivo drug clearance from in vitro data. D Potential inter-ethnic differences. Xenobiotica 36 499-513... 

Scott RC, Ramsay JD (1987) Comparison of the in vivo and in vitro percutaneous absorption of a lipophilic molecule (cypermethrin, a pyrethroid insecticide). J Invest Dermatol 89 142-146 Serat WF (1973) Calculation of a safe reentry time into an rachaid treated with a pesticide chemical which produces a measiuable physiological response. Arch Environ Contam Toxicol 1 170-181 Serat WF, Bailey JB (1974) Estimating the relative toxicologic potential of each pesticide in mixture of residues on foliage. Bull Environ Contam Toxicol 12 682-686 Serat WF, Mengle DC, Anderson HP, Kahn E (1975) On the estimation of worker entry intervals into pesticide treated fields with and without the exposure of human subjects. Bull Environ Contam Toxicol 13 506-512... 

Pyrethroids, such as p,p -DDT, are toxic because they interact with Na+ channels of the axonal membrane, thereby disturbing the transmission of nerve action potential (Eldefrawi and Eldefrawi 1990, and Chapter 5, Section 5.2.4 of this book). In both cases, marked hydrophobicity leads to bioconcentration of the insecticides in the axonal membrane and reversible association with the Na+ channel. Consequently, both DDT and pyrethroids show negative temperature coefficients in arthropods increasing temperature brings decreasing toxicity because it favors desorption of insecticide from the site of action. 

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... 

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