F E A T U R E Active Insight: In this series, the chemistry of major groups will be examined Steve Broadbent

ipronil is a broad-spectrum phenyl- the GABA channel from operating normally. insecticide that has widespread uses in In vitro assays have shown that the GABA receptors professional pest management for the F of insects are more sensitive to the action of fipronil control of termites, cockroaches, and ants. This than those in mammals. It has also been shown group of also contains acetoprole, that fipronil may act at the insect L-glutamate- ethiprole, pyrofluprole, pyriprole, and vaniliprole. gated chloride channel, which is not present in Fipronil was first synthesised by Rhône-Poulenc vertebrate nervous systems. This helps explain in France during 1987, and received its first the greater toxicity of fipronil in insects relative to registrations in 1993. In 2003, the commercial its toxicity to mammals. Two fipronil metabolites rights to fipronil were acquired by Bayer, including (break-down products) of mammals and plants a wide range of fipronil manufacturing process (fipronil sulfone and fipronil sulphide), and the patents and usage/application patents. Because major photodegradation product (desulphinyl of concerns about competition, several countries fipronil), are also believed to act in a similar way to required Bayer to sell the rights to commercialise the parent fipronil molecule at the GABA receptors. fipronil to other parties. In these countries, the This likely explains its greater residual performance commercial rights were purchased by BASF. Fipronil in soil, enhancing its termiticidal properties. is now off-patent, which has seen many other entrants in the market. To understand the fipronil mode of action better, we need to further explore the insect nervous Technical grade fipronil is a white solid with system. In the last issue of the FAOPMA Magazine the chemical name (IUPAC): (+)-5-amino-1-(2,6- (July 2019), when discussing the mode of action dichloro-alpha,alpha,alpha-trifluoro-p-tolyl)-4- of the , we looked at how the message trifluoromethylsulfinylpyrazole-3-carbonitrile. travels along the nerve axon (fibre) as an electrical In insects, fipronil has both contact and ingestion impulse. activity, but is particularly effective by way of A gap, correctly called a synapse or synaptic ingestion. Fipronil is a nervous system poison cleft, separates the axon of one neuron from the that causes excitation and convulsions in dendrites of the next neuron. The electrical impulse insects, leading to death. Fipronil (and one of its must cross this gap to continue on its path. This breakdown products) affects the central nervous occurs through chemical changes. system of insects by preventing the passage of chloride ions into the nerve cells through either At the end of the axon from which the electrical the GABA-receptor (gamma-aminobutyric acid) or impulse is coming, the membrane depolarizes one of two glutamate-gated chloride channels. In and gated-ion channels open, allowing calcium short, the presence of three different target sites ions (Ca2+) to enter the neuron. When the calcium in insects explains why it is so potent. It is often ions rush in, a chemical called a neurotransmitter referred to as a GABA-antagonist since it prevents (e.g. acetylcholine) is released into the synapse.

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The neurotransmitter chemical moves across the Fipronil has been shown to be stable in acid and synapse and binds to proteins on the neuron neutral solutions, but under alkaline conditions membrane that’s about to receive the impulse/ degradation increases in direct proportion to the message. These proteins serve as receptors, and rise in pH. Degradation of fipronil at pH 12 was 300 different proteins serve as receptors for different times faster than at pH 9. Fipronil is not volatile and neurotransmitters. tends to break down relatively quickly in sunlight; however, it is stable in water and has a half-life in After the neurotransmitter produces its effect, soil of up to a year, favouring its use for long-term which can either be excitation or inhibition, the control of termites. Fipronil is not highly water receptor lets go of it, and the neurotransmitter soluble and it tightly adsorbs to soil, which reduces goes back into the synapse. In the synapse, the the opportunity for leaching to ground water and cell ‘recycles’ the degraded neurotransmitter. The runoff to surface waters, characteristics that further chemicals go back into the nerve membrane so its attractiveness as a soil termiticide.  that, during the next impulse, when the synaptic vesicles bind to the membrane, the complete This article first appeared inProfessional Pest neurotransmitter can again be released. Manager.

When fipronil is present in the insect system, it Steve Broadbent is the Regional Director, Australia, prevents the calcium ions entering the neuron to SE Asia, South Africa & Gulf Region, Ensystex, release these neurotransmitters. Thus, it blocks the Australia. calcium channel causing hyperpolarisation and the Email: [email protected] excitory effects we mentioned above.

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