title: Minireview: Mode of action of meta-diamide insecticides.
abstract: Meta-diamides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of RDL GABA receptor noncompetitive antagonists showing high insecticidal activity against Spodoptera litura. The mode of action of the meta-diamides was demonstrated to be distinct from that of conventional noncompetitive antagonists (NCAs) such as fipronil, picrotoxin, lindane, dieldrin, and α-endosulfan. It was suggested that meta-diamides act at or near G336 in the M3 region of the Drosophila RDL GABA receptor. Although the site of action of the meta-diamides appears to overlap with that of macrocyclic lactones including avermectins and milbemycins, differential effects of mutations on the actions of the meta-diamides and the macrocyclic lactones were observed. Molecular modeling studies revealed that the meta-diamides may bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor better when in the closed state, which is distinct from the NCA-binding site, which is in a channel formed by M2s. In contrast, the macrocyclic lactones were suggested to bind to an inter-subunit pocket near G336 in the Drosophila RDL GABA receptor when in the open state. Furthermore, mechanisms underlying the high selectivity of meta-diamides are discussed. This minireview highlights the unique features of novel meta-diamide insecticides and demonstrates why meta-diamides are anticipated to become prominent insecticides that are effective against pests resistant to cyclodienes and fipronil.
authors.affiliation: Agrochemicals Research Center, Mitsui Chemicals Agro, Inc., Mobara, Chiba 297-0017, Japan. Electronic address: Toshifumi.Nakao@mitsui-chem.co.jp.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nakao
authors.affiliation: Agrochemicals Research Center, Mitsui Chemicals Agro, Inc., Mobara, Chiba 297-0017, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Banba
mesh_terms: D000818:Animals; D003958:Diamide / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D062105:Molecular Docking Simulation; D009154:Mutation; D011720:Pyrazoles / Q000494:pharmacology; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D019476:Insect Proteins; D007306:Insecticides; D007783:Lactones; D011720:Pyrazoles; D018079:Receptors, GABA; D003958:Diamide; C082360:fipronil
keywords: A2′ mutation; Insecticide; Meta-diamide; RDL GABA receptor