Abstract
Novel meta-diamide insecticides [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamides] are a distinct class of insect RDL GABA receptor antagonists that have been suggested to act at or near G336 in the M3 region of the Drosophila RDL GABA receptor. Here, we demonstrate the low-level antagonist activities of novel meta-diamides against the human GABA type A receptor (GABAAR) α1β2γ2S, mammalian GABAAR α1β3γ2S, and the human glycine receptor (GlyR) α1β. The Gly residue at position 336 in the M3 region of the Drosophila RDL GABA receptor is essential for its high sensitivity to meta-diamides. Therefore, the effects of an equivalent mutation (A288G) in human GlyR α1 on the antagonist activities of meta-diamides were studied. The A288G mutation dramatically increased the antagonist activities of meta-diamides against GlyR α1. Thus, A288 in GlyR α1 is important for this receptor’s sensitivity to meta-diamide insecticides. Our study is useful for understanding the mechanisms underlying meta-diamide selectivity.
