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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Fipronil is a potent open channel blocker of glutamate-activated chloride channels in cockroach neurons.

Fipronil, a phenylpyrazole insecticide, displays high insecticidal activity and reduced mammalian toxicity. To better elucidate the mechanism of its selective toxicity between insects and mammals and activity against dieldrin-resistant insects, we studied fipronil action on glutamate-gated chloride channels (GluCls), unique invertebrate ligand-gated chloride channels, in cockroach thoracic ganglion neurons, using the whole-cell patch clamp technique. Glutamate evoked two types of chloride currents, a desensitizing current and a nondesensitizing current. Fipronil differentially inhibited these two types of currents with different potencies and with different rates of reversibility. Fipronil inhibited the desensitizing and nondesensitizing GluCls with IC50 values of 801 and 10 nM, respectively. Kinetic analysis revealed that fipronil blocks required channel opening. Recovery of the desensitizing current from fipronil block required channel opening, whereas recovery of nondesensitizing current from block was independent of channel opening. The high potency of fipronil against the nondesensitizing current was due to a slow unblocking rate constant. In addition, when the nondesensitizing GluCls were occupied by picrotoxinin, the receptors became less sensitive to fipronil block. It is concluded that GluCls are a critical target for fipronil, especially for the selective toxicity between mammals and insects, and that fipronil block of GluCls may play a role in the lack of the cross-resistance with dieldrin.[1]


  1. Fipronil is a potent open channel blocker of glutamate-activated chloride channels in cockroach neurons. Zhao, X., Yeh, J.Z., Salgado, V.L., Narahashi, T. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
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