Fipronil binding site

One important group of insecticides, the avermectins, works differently by being agonists and not antagonists as the other, acting on the chloride channels. The avermectins are produced by Streptomyces avermitilies. The binding site is different, and cross-resistance to fipronil, the cyclodienes, and lindane does not seem to occur. The toxic symptoms in insects and mammals are different. Mammals poisoned with avermectins exhibit hyperexcitability, incoordination, and tremor followed by ataxia and paralysis. In insects and nematodes, the hyperexcitation phase is absent. Their symptoms are... 

Fig. 29.5.4. Possible binding interactions of fipronil with side chains of residues A2, T6 and L9 in the NCA site. Fipronil was docked into a model of the NCA binding site of a homopentameric mammalian CABAa-jSj receptor, after Ref [64], using the Schrddinger Suite 2006 Induced Fit Docking protocol Clide version 4.0, Schrddinger, LLC, New York, 2005 Prime version 1.5, Schrddinger, LLC, New York, 2005.

Figure 8. A Model of the Binding Site for Noncompetitive GABA Receptor Antagonists. The Orientation of Fipronil Remains to Be Determined.

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