Diamide insecticides
Class of insecticide
From Wikipedia, the free encyclopedia
Diamide insecticides are a class of insecticides, active mainly against lepidoptera (caterpillars), which act on the insect ryanodine receptor. They are diamides of either phthalic acid or anthranilic acid, with various appropriate further substitutions.[1][2]
Worldwide sales of diamides in 2018 were estimated at US$2.4 billion, which is 13% of the $18.4 billion insecticide market.[3]
History and examples
The first diamide was flubendiamide. It was invented by Nihon Nohyaku and commercialised in 2007.[1] It is a highly substituted diamide of phthalic acid and is highly active against lepidoptera (caterpillers).[1][2] Later DuPont introduced chlorantraniliprole, which is more active against caterpillers and in addition active against other insect types.[1][2] Cyanthraniliprole, introduced later, shows systemic activity and is also active against sucking pests such as aphids and whitefly.[2]
According to one review, the first species reported to show resistance to diamides was the diamondback moth in 2012.[4]
The following diamides have been given ISO common names.[5] Flubendiamide and cyhalodiamide are phthalic[6] diamides.[5] Chlorantraniliprole, cyantraniliprole, cyclaniliprole, fluchlordiniliprole, pioxaniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole are anthranilic[7] diamides.[5] Eight diamide insecticides have been commercialized as of February 2023.[2]
Mechanism of action
Diamides selectively activate insect ryanodine receptors (RyR), which are large tetrameric ryanodine-sensitive calcium release channels present in the sarcoplasmic reticulum and endoplasmic reticulum in neuromuscular tissues.[8] The ryanodine receptor is also the target of the alkaloid insecticide ryanodine, after which it is named, although it addresses a different binding site on the receptor.[8] A 3.2-Å structure of cyanthraniliprole bound to a ryanodine receptor has been determined, which informs on the mechanism of action as well as various mutations causing resistance.[2]
The binding of diamides or ryanodine to the calcium channels causes them to remain open, leading to the loss of calcium crucial for biological processes.[9] Specifically, calcium release is essential for muscle contraction and therefore locomotion.[10] Ryanodine receptors are the only major calcium release channels of the sarco/endoplasmic reticulum.[10] The forcing open of these channels then causes insects to act lethargic, stop feeding, and eventually die.[9]
Toxicity
Diamides show low acute mammalian toxicity and appear to safe for bees.[12]
A metabolite of flubendiamide is very persistent and toxic to aquatic invertebrates, causing flubendiamide to be banned by the United States EPA.[13]