Abstract
Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.
Highlights
Gamma-aminobutyric acid (GABA) is present in both mammals and invertebrates and is an important inhibitory neurotransmitter [1]
In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 values of
Isoxazolines and meta-diamides have emerged as second-generation GABAergic compounds in the search for novel insecticides [7]
Summary
Gamma-aminobutyric acid (GABA) is present in both mammals and invertebrates and is an important inhibitory neurotransmitter [1]. Among the different types of GABA receptors, the GABA receptor-chloride channel complex is an important target site for insecticides, such as lindane and fipronil [2]. Development of insecticides that work on novel binding sites of this receptor could help avoid cross resistance problems and contribute to effective control of pest insects. Fluralaner (Figure 1) and afoxolaner, were developed by scientists from Nissan Chemical Industries in Japan and DuPont in the U.S, respectively [8,9]. Both compounds have been approved by the U.S Food and Drug
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