AbstractBACKGROUNDFluralaner, a novel pesticide that targets the γ‐aminobutyric acid (GABA) receptor (GABAR) subunit of resistant to dieldrin (RDL), exhibits strong potential to be an insecticide to control agricultural insect pests. However, the risk and action of fluralaner to economic insects, e.g., honeybee Apis mellifera Linnaeus, remains unclear.RESULTSIn this study, both oral and contact toxicity of fluralaner to honeybee were found to be 0.13 μg adult–1. Abamectin, dieldrin, ethiprole, α‐endosulfan, fipronil and fluralaner strongly inhibited the GABA‐induced current in A. mellifera RDL (AmRDL), expressed in Xenopus laevis oocytes, with median inhibitory concentration (IC50) values of 7.99, 868.1, 27.10, 412.0, 11.21 and 13.59 nM, respectively. The binding free energy and electrophysiological response of AmRDL and insecticides were opposite. The correlation values between toxicity (to A. mellifera) and binding free energy/electrophysiological inhibition (to AmRDL) were at a moderate level.CONCLUSIONIn conclusion, we report for the first time the notable risk of fluralaner to honeybee in vivo and compared the actions of GABAR‐targeted insecticides on the AmRDL receptor. © 2019 Society of Chemical Industry