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

Abstract

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.

Modes of Action, Resistance and Toxicity of Insecticides Targeting Nicotinic Acetylcholine Receptors

“…Sulfoxaflor binds to the orthosteric (agonist) site on insect nAChRs competing directly with the neurotransmitter ACh. Binding causes uncontrolled neuronal firing resulting in muscle tremors followed by paralysis and death [36]. Thus sulfoximines bind to the orthosteric binding site and show agonist [37] and rapidly desensitizing [38] actions.…”

“…Development of resistance is a major problem for all insecticides [36] and is perhaps one of the best examples of natural selection in action. Discussion here is confined to neonicotinoid resistance because of its high significance.…”

Resistance to neurotoxic insecticides in populations of the coffee leafminer Leucoptera coffeella

“…ha -1 ) cause high mortality to L. coffeella; moreover, it is selective for wasps [26]. Selectivity is an important factor in managing resistance in pest insects [27]. Many studies with basic lines of susceptibility have been done with chlorantraniliprole insecticide and Lepidoptera, and the observations are that populations show susceptibility with low variation in mortality [28,29].…”

Toxicity of Neonicotinoids to Honey Bees and Detoxification Mechanism in Honey Bees

“…In some cases though the chemical is directly not toxic to honeybees it may affect some of the behavioral symptoms like loss of memory, which leads to colony collapse disorder (CCD) which is one of the indirect effect to honeybees. Some of the major metabolites of neonicotinoids are equally neurotoxic, acting on the same receptors (Suchail et (Casida et al, 2013) and imidacloprid is the second most widely used agrochemical in the world (Pollak, 2011).…”