The double-edged sword of ion channel-targeting pesticides: a paradigm shift from health risks to precision intervention

Abstract

Amidst the dual challenges of global food security and ecological security, the development of highly effective and low-risk green pesticides has become a critical pathway for promoting sustainable agricultural development. This review systematically summarizes the dual characteristics of novel pesticides targeting ion channels in precise pest control and ecological risk management. Research indicates that due to the high evolutionary conservation of ion channels in insects and mammals, pesticides exhibit cross-species similarity in their actions. This characteristic is key to understanding the broad toxicity of pesticides and also provides molecular targets for designing universal detoxification intervention strategies. By reviewing the regulatory mechanisms of typical pesticides such as pyrethroids and diamides on key ion channels like voltage-gated sodium channels and ryanodine receptors, we revealed their double-edged sword effect of "high efficacy coexisting with potential risks": while achieving precise insecticide action, they may induce neurotoxicity or endocrine disruption in non-target organisms due to the structural conservation of channels. Based on mechanistic toxicological analysis, this review further proposes novel intervention strategies centered on "reversible toxicity", including the use of computational toxicology for early risk warning, structure-guided molecular design to reduce cross-reactivity with mammalian channels, and the development of channel-specific antagonists and allosteric modulators as precise detoxification methods, thereby constructing a toxicity-blocking system covering the entire chain from "molecular recognition to clinical intervention". Through the multidimensional integration of intelligent delivery systems, comprehensive resistance management, and full life-cycle risk management, these strategies are expected to promote the formation of a new generation of pesticide research and development paradigm characterized by "efficacy-toxicity separation," providing theoretical support for harmonizing agricultural pest control and public health protection.

Keywords: Cross-species toxicity; Double-edged sword; Highly effective; Ion channel-targeting pesticides; Toxicity management.