Fipronil chloride channel

More recently, the new insecticide, fipronil (Figure 3.11), has been shown to act as a potent blocker of the GABA-regulated chloride channel. It is being used to control both foliar and soil insects9 whilst the avermectins and milbemycins can only be used against foliar pests. 

Cyflumetofen [198] is an experimental acaricide/miticide for use in vegetables and fruits. Pyriprole and pyrafluprole are two experimental insecticides introduced by Nihon Nohyaku and related, both in chemistry and mode of action to the highly successful insecticide fipronil. Fipronil acts at the GABA receptor to block the chloride channel. 

Figure 7.21 Effects of fipronil on the GABA response in Xenopus oocytes showing that fipronil interferes with passage of chloride ions through the GABA-regulated chloride channel. (From Gant, D.B. et al., Rev. Toxicol., 2,141,1998. With permission.)...

Zhao X, Yeh JZ, Salgado VL, and Narahashi T (2004) Fipronil is a potent open channel blocker of glutamate-activated chloride channels in cockroach neurons. The Journal of Pharmacology and Experimental Therapeutics 310 192-201. 

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... 

Fipronil and its predominant sulfone metabolite are unique among insecticides in that they have three known high-affinity target sites - the three ligand-gated chloride channels that mediate most inhibitory transmission in the insect nervous system GABA receptors and the two subtypes of GluCls that have been de-... 

Soon after the development of fipronil was announced in 1992 [8], its mode of action as an NCA of GABA-gated chloride channels was published. Fipronil and other insectiddal phenylpyrazoles were observed to cause symptoms in house flies and mice that were similar to those of the known GABA antagonists dieldrin... 

Two histamine-gated chloride chatmd subunits (HisQl and HisCl2, Fig. 29.5.3) expressed in Drosophila eye both contain T at position 2 and are insensitive to PTX and fipronil [58]. In addition, two novel proton-gated chloride channel subunits in this family (pHClA, B and C in Fig. 29.5.3), of unknown function, both contain M at position 2 and are also insensitive to PTX and fipronil [59]. 

Fipronil as an insecticide was first introduced by Rhone Poulenc Agro in 1993. It is also used for termite and fruit fly control in Australia and throughout the Pacific Region, but not registered yet in the U.S. for that use. Fipronil acts by blocking the chloride channels in the central nervous system (1) and is very effective in the case of flea control on pets (2,3) and wild animals (4). Its... 

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