Bifenazate is a very selective acaricide that controls the spider mite, Tetranychus urticae. Bifenazate is the first example of a carbazate acaricide. Its mode of action remains unclear. Bifenazate and its active metabolite diazene induce paralysis in spider mites, suggesting that they may act on the nervous system. Here we have employed a homologue (TuGABAR) of RDL (Resistance to dieldrin), a subunit of ionotropic γ-aminobutyric acid (GABA) receptor, from T. urticae to investigate the action of bifenazate and its active metabolite diazene on this receptor function. Although neither acaricide showed a GABA agonist action, 30 μM of bifenazate or diazene significantly enhanced the GABA-induced response of TuGABAR in a dose-dependent manner, shifting the EC(50) of GABA from 24.8 μM to 4.83 μM and 10.8 μM, respectively. This action demonstrates a positive allosteric modulator effect of bifenazate on T. urticae GABA receptors. This synergistic action is likely the result of bifenazate binding to a site distinct from that of the GABA binding site causing a conformational change that affects the magnitude of the GABA response. Precisely how the observed GABA synergist action correlates with the acaricidal activity of bifenazate, if at all, has yet to be determined.
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