Differential mechanisms of action of the novel γ-aminobutyric acid receptor antagonist ectoparasiticides fluralaner (A1443) and fipronil

BACKGROUND: Fluralaner (A1443) is an isoxazoline ectoparasiticide that is a novel antagonist of gamma-aminobutyric acid (GABA) receptors (GABARs), with a potency comparable to that of fipronil, a phenylpyrazole ectoparasiticide. To clarify the biological effectiveness of fluralaner against fipronil-resistant pests, differences in the actions of fluralaner and fipronil on GABARs that possess resistance to dieldrin (rdl)-type mutations were evaluated. RESULTS: Fipronil had neither pest control nor GABAR-antagonistic activities against two-spotted spider mites (Tetranychus urticae) that had two different rdl-type amino acids (A(301) -> H and T-350 -> A: Drosophila melanogaster GABAR numbering) and against small brown planthoppers (Laodelphax striatellus) that had a novel rdl-type (A(283) -> N) mutation in GABARs. In contrast, fluralaner showed not only high pest control activities against these pests, but also excellent antagonistic activities for these rdl-type GABARs. CONCLUSION: The findings indicate that rdl-type fipronil-resistant pests do not show cross-resistance to fluralaner owing to the differential actions of fluralaner and fipronil on the GABAR. (C) 2014 Society of Chemical Industry