Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances
Synthetic pyrethroid insecticides were introduced into widespread use for the control of insect pests and disease vectors more than three decades ago. In addition to their value in controlling agricultural pests, pyrethroids are at the forefront of efforts to combat malaria and other mosquito-borne diseases and are also common ingredients of household insecticide and companion animal ectoparasite control products. The abundance and variety of pyrethroid uses contribute to the risk of exposure and adverse effects in the general population. The insecticidal actions of pyrethroids depend on their ability to bind to and disrupt voltage-gated sodium channels of insect nerves. Sodium channels are also important targets for the neurotoxic effects of pyrethroids in mammals but other targets, particularly voltage-gated calcium and chloride channels, have been implicated as alternative or secondary sites of action for a subset of pyrethroids. This review summarizes information published during the past decade on the action of pyrethroids on voltage-gated sodium channels as well as on voltage-gated calcium and chloride channels and provides a critical re-evaluation of the role of these three targets in pyrethroid neurotoxicity based on this information.
KeywordsPyrethroid Insecticide Neurotoxicity Voltage-gated sodium channel Voltage-gated calcium channel Voltage-gated chloride channel
Research that was conducted in the author’s laboratory and the preparation of this review were supported by grants from National Institute of Environmental Health Sciences, National Institutes of Health (R01-ES08962 and R01-ES013686) and the Pyrethroid Working Group, a consortium of firms (Bayer CropScience, DuPont Crop Protection, FMC Corporation, Syngenta Crop Protection Inc., and Valent Corporation) that market pyrethroid-based insecticide products in the United States. The contents of this paper are solely the responsibility of the author and do not necessarily represent the official views of any of the sponsors.
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