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Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)

Recent studies suggest that N, N-diethyl-meta-toluamide (DEET) is an acetylcholinesterase inhibitor and that this action may result in neurotoxicity and pose a risk to humans from its use as an insect repellent. We investigated the mode of action of DEET neurotoxicity in order to define the specific...

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Autores principales: Swale, Daniel R., Sun, Baonan, Tong, Fan, Bloomquist, Jeffrey R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125160/
https://www.ncbi.nlm.nih.gov/pubmed/25101788
http://dx.doi.org/10.1371/journal.pone.0103713
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author Swale, Daniel R.
Sun, Baonan
Tong, Fan
Bloomquist, Jeffrey R.
author_facet Swale, Daniel R.
Sun, Baonan
Tong, Fan
Bloomquist, Jeffrey R.
author_sort Swale, Daniel R.
collection PubMed
description Recent studies suggest that N, N-diethyl-meta-toluamide (DEET) is an acetylcholinesterase inhibitor and that this action may result in neurotoxicity and pose a risk to humans from its use as an insect repellent. We investigated the mode of action of DEET neurotoxicity in order to define the specific neuronal targets related to its acute toxicity in insects and mammals. Although toxic to mosquitoes (LD(50) ca. 1.5 µg/mg), DEET was a poor acetylcholinesterase inhibitor (<10% inhibition), even at a concentration of 10 mM. IC(50) values for DEET against Drosophila melanogaster, Musca domestica, and human acetylcholinesterases were 6–12 mM. Neurophysiological recordings showed that DEET had excitatory effects on the housefly larval central nervous system (EC(50): 120 µM), but was over 300-fold less potent than propoxur, a standard anticholinesterase insecticide. Phentolamine, an octopamine receptor antagonist, completely blocked the central neuroexcitation by DEET and octopamine, but was essentially ineffective against hyperexcitation by propoxur and 4-aminopyridine, a potassium channel blocker. DEET was found to illuminate the firefly light organ, a tissue utilizing octopamine as the principal neurotransmitter. Additionally, DEET was shown to increase internal free calcium via the octopamine receptors of Sf21 cells, an effect blocked by phentolamine. DEET also blocked Na(+) and K(+) channels in patch clamped rat cortical neurons, with IC(50) values in the micromolar range. These findings suggest DEET is likely targeting octopaminergic synapses to induce neuroexcitation and toxicity in insects, while acetylcholinesterase in both insects and mammals has low (mM) sensitivity to DEET. The ion channel blocking action of DEET in neurons may contribute to the numbness experienced after inadvertent application to the lips or mouth of humans.
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spelling pubmed-41251602014-08-12 Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET) Swale, Daniel R. Sun, Baonan Tong, Fan Bloomquist, Jeffrey R. PLoS One Research Article Recent studies suggest that N, N-diethyl-meta-toluamide (DEET) is an acetylcholinesterase inhibitor and that this action may result in neurotoxicity and pose a risk to humans from its use as an insect repellent. We investigated the mode of action of DEET neurotoxicity in order to define the specific neuronal targets related to its acute toxicity in insects and mammals. Although toxic to mosquitoes (LD(50) ca. 1.5 µg/mg), DEET was a poor acetylcholinesterase inhibitor (<10% inhibition), even at a concentration of 10 mM. IC(50) values for DEET against Drosophila melanogaster, Musca domestica, and human acetylcholinesterases were 6–12 mM. Neurophysiological recordings showed that DEET had excitatory effects on the housefly larval central nervous system (EC(50): 120 µM), but was over 300-fold less potent than propoxur, a standard anticholinesterase insecticide. Phentolamine, an octopamine receptor antagonist, completely blocked the central neuroexcitation by DEET and octopamine, but was essentially ineffective against hyperexcitation by propoxur and 4-aminopyridine, a potassium channel blocker. DEET was found to illuminate the firefly light organ, a tissue utilizing octopamine as the principal neurotransmitter. Additionally, DEET was shown to increase internal free calcium via the octopamine receptors of Sf21 cells, an effect blocked by phentolamine. DEET also blocked Na(+) and K(+) channels in patch clamped rat cortical neurons, with IC(50) values in the micromolar range. These findings suggest DEET is likely targeting octopaminergic synapses to induce neuroexcitation and toxicity in insects, while acetylcholinesterase in both insects and mammals has low (mM) sensitivity to DEET. The ion channel blocking action of DEET in neurons may contribute to the numbness experienced after inadvertent application to the lips or mouth of humans. Public Library of Science 2014-08-07 /pmc/articles/PMC4125160/ /pubmed/25101788 http://dx.doi.org/10.1371/journal.pone.0103713 Text en © 2014 Swale et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Swale, Daniel R.
Sun, Baonan
Tong, Fan
Bloomquist, Jeffrey R.
Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)
title Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)
title_full Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)
title_fullStr Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)
title_full_unstemmed Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)
title_short Neurotoxicity and Mode of Action of N, N-Diethyl-Meta-Toluamide (DEET)
title_sort neurotoxicity and mode of action of n, n-diethyl-meta-toluamide (deet)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4125160/
https://www.ncbi.nlm.nih.gov/pubmed/25101788
http://dx.doi.org/10.1371/journal.pone.0103713
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