title: Differential mechanisms of action of the novel γ-aminobutyric acid receptor antagonist ectoparasiticides fluralaner (A1443) and fipronil.
abstract: BACKGROUND
  Fluralaner (A1443) is an isoxazoline ectoparasiticide that is a novel antagonist of γ-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biological Research Laboratories, Nissan Chemical Industries Ltd, Shiraoka Saitama, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Asahi
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsui
authors.forename: Kunimitsu
authors.initials: K
authors.lastname: Nakahira
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D018756:GABA Antagonists; D006430:Hemiptera; D007555:Isoxazoles; D008969:Molecular Sequence Data; D011720:Pyrazoles; D040102:Tetranychidae; D018675:Toxicity Tests; D014981:Xenopus
chemical_list: C000591860:A1443 compound; D018756:GABA Antagonists; D007555:Isoxazoles; D011720:Pyrazoles; C082360:fipronil
keywords: A1443; GABA; fluralaner; ligand-gated ion channel; parasiticide; receptor