Neuroactive Insecticides: Targets, Selectivity, Resistance, and Secondary Effects

• Published in: Annual review of entomology 2013-01, Vol.58 (1), p.99-117
• Main Authors: Casida, John E, Durkin, Kathleen A
• Format: Article
• Language: English
• Subjects: acetylcholinesterase; Alzheimer Disease - chemically induced; Animal, plant and microbial ecology; Animals; Applied ecology; Biological and medical sciences; calcium channels; Chemical control; Control; Ecotoxicology, biological effects of pollution; Effects of pollution and side effects of pesticides on vertebrates; Fundamental and applied biological sciences. Psychology; GABA; Humans; Insecta - drug effects; Insecticides - toxicity; Mammalia; Mammals - metabolism; Medical sciences; nicotinic receptor; Parkinson Disease - etiology; Pesticides, fertilizers and other agrochemicals toxicology; Phytopathology. Animal pests. Plant and forest protection; Protozoa. Invertebrates; Rats; receptor; secondary targets; sodium channel; Species Specificity; Toxicology
• ISSN: 0066-4170; 1545-4487
• DOI: 10.1146/annurev-ento-120811-153645

Neuroactive insecticides are the principal means of protecting crops, people, livestock, and pets from pest insect attack and disease transmission. Currently, the four major nerve targets are acetylcholinesterase for organophosphates and methylcarbamates, the nicotinic acetylcholine receptor for neonicotinoids, the γ-aminobutyric acid receptor chloride channel for polychlorocyclohexanes and fiproles, and the voltage-gated sodium channel for pyrethroids and dichlorodiphenyltrichloroethane. Species selectivity and acquired resistance are attributable in part to structural differences in binding subsites, receptor subunit interfaces, or transmembrane regions. Additional targets are sites in the sodium channel (indoxacarb and metaflumizone), the glutamate-gated chloride channel (avermectins), the octopamine receptor (amitraz metabolite), and the calcium-activated calcium channel (diamides). Secondary toxic effects in mammals from off-target serine hydrolase inhibition include organophosphate-induced delayed neuropathy and disruption of the cannabinoid system. Possible associations between pesticides and Parkinson's and Alzheimer's diseases are proposed but not established based on epidemiological observations and mechanistic considerations.