The mode of action of isocycloseram: A novel isoxazoline insecticide

Isocycloseram is a novel isoxazoline insecticide and acaricide with activity against lepidopteran, hemipteran, coleopteran, thysanopteran and dipteran pest species. Isocycloseram selectively targets the invertebrate Rdl GABA receptor at a site that is distinct to fiproles and organochlorines. The widely distributed cyclodiene resistance mutation, A301S, does not affect sensitivity to isocycloseram, either in vitro or in vivo, demonstrating the suitability of isocylsoseram to control pest infestations with this resistance mechanism. Detailed studies demonstrated that the binding sites relevant to the insecticidal activity of avermectins and isocycloseram are distinct. Isocycloseram was shown to compete for binding with metadiamide insecticides related to broflanilide. In addition, a G335M mutation in the third transmembrane domain of the Rdl GABA receptor, impaired the ability of both isocycloseram and metadiamides to block the GABA mediated response. As such the Insecticides Resistance Action Committee (IRAC) has classified isocycloseram in Group 30 “GABA-Gated Chloride Channel Allosteric Modulators”. [Display omitted] •Isocycloseram is a novel insecticide of the isoxazoline class.•It is a potent inhibitor of insect GABA gated chloride channel function.•It retains efficacy against insects carrying the A301S resistance mutation.•Its effects are distinct from those of organochlorines, fiproles and avermectin.•It is grouped with isoxazolines and metadiamides for resistance management.