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Mode of action of N,N-Diethyl-meta-Toluamide (DEET) on the insect nervous system
We have confirmed that DEET is lethal to mosquitoes at topical doses in the microgram range (2-4 mg), but observe that DEET is an extremely poor AChE inhibitor in mosquitoes (<10% inhibition), even at a concentration of 10 mM. AChE enzymes from human, Drosophila melanogaster, and Musca domestica are slightly more sensitive with IC50 values approaching 10 mM, an unrealistic concentration through any natural route of exposure.
Neurophysiological recordings were performed to determine the effect of DEET on insect central nervous system electrical discharge rates. DEET was found to have neuroexcitatory effects on the CNS in the millimolar range (EC50: 1.2 mM), over 1000-fold less potent than registered anticholinesterases, such as Propoxur. Lidocaine, a known voltage-sensitive sodium channel blocker, was found to have inhibitory effects on Musca domestica CNS (EC50: 2.6 mM), suggesting DEET has a different mode of action.
In conclusion, while DEET shows anticholinesterase properties in adult mosquitoes and insect CNS recordings, the high concentrations needed to yield intoxication suggests it is unlikely that anticholinesterase effects would be of relevance to human toxicity.
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