+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Fluxametamide: A novel isoxazoline insecticide that acts via distinctive antagonism of insect ligand-gated chloride channels

Fluxametamide: A novel isoxazoline insecticide that acts via distinctive antagonism of insect ligand-gated chloride channels

Pesticide Biochemistry and Physiology 151: 67-72

Fluxametamide is a novel wide-spectrum insecticide that was discovered and synthesized by Nissan Chemical Industries, Ltd. To identify the mode of action of fluxametamide, we first performed [3H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) binding assays. Fluxametamide potently inhibited the specific binding of [3H]EBOB to housefly-head membranes, suggesting that fluxametamide affects insect γ-aminobutyric acid (GABA)-gated chloride channels (GABACls). Next, the antagonism of housefly GABACls and glutamate-gated chloride channels (GluCls) was examined using the two-electrode voltage clamp (TEVC) method. Fluxametamide inhibited agonist responses in both ion channels expressed in Xenopus oocytes in the nanomolar range, indicating that this insecticide is a ligand-gated chloride channel (LGCC) antagonist. The insecticidal and LGCC antagonist potencies of fluxametamide against fipronil-susceptible and fipronil-resistant strains of small brown planthoppers and two-spotted spider mites, which are insensitive to fipronil, were evaluated. Fluxametamide exhibited similar levels of both activities in these fipronil-susceptible and fipronil-resistant arthropod pests. These data indicate that fluxametamide exerts distinctive antagonism of arthropod GABACls by binding to a site different from those for existing antagonists. In contrast to its profound actions on the arthropod LGCCs, the antagonistic activity of fluxametamide against rat GABACls and human glycine-gated chloride channels was nearly insignificant, suggesting that fluxametamide has high target-site selectivity for arthropods over mammals. Overall, fluxametamide is a new type of LGCC antagonist insecticide with excellent safety for mammals at the target-site level.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 066446796

Download citation: RISBibTeXText

PMID: 30704715

DOI: 10.1016/j.pestbp.2018.02.002

Related references

The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels. Biochemical and Biophysical Research Communications 391(1): 744-749, 2010

Evolutionary relationship of the ligand-gated ion channels and the avermectin-sensitive, glutamate-gated chloride channels. Journal Of Molecular Evolution. 44(5): 501-508, 1997

The novel isoxazoline ectoparasiticide lotilaner (Credelio™): a non-competitive antagonist specific to invertebrates γ-aminobutyric acid-gated chloride channels (GABACls). Parasites and Vectors 10(1): 530, 2018

The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochemistry and Molecular Biology 45: 111-124, 2014

Functional modifications of acid-sensing ion channels by ligand-gated chloride channels. Plos One 6(7): E21970, 2011

The role of voltage-gated chloride channels in type II pyrethroid insecticide poisoning. Toxicology and Applied Pharmacology 163(1): 1-8, 2000

Insect olfactory receptors are heteromeric ligand-gated ion channels. Nature (London) 452(7190): 1002, 2008

Detection of ligand gated chloride channels on human leukocytes. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 568 7, 2003

Fipronil blocks invertebrate ligand-gated chloride channels. Society for Neuroscience Abstracts 25(1-2): 1483, 1999

Chloro-Plt-I A spider toxin that activates ligand-gated chloride channels. Biophysical Journal 78(1 Part 2): 353A, 2000

A high-throughput assay for modulators of ligand-gated chloride channels. Assay and Drug Development Technologies 3(1): 59-64, 2005

Ligand-gated chloride channels are receptors for biogenic amines in C. elegans. Science 325(5936): 96-100, 2009

Functional diversity of GABAA receptor ligand-gated chloride channels in rat synaptoneurosomes. Synapse 19(3): 188-196, 1995

A histamine receptor in the insect visual system is a ligand gated chloride channel. Society for Neuroscience Abstracts 15(1): 26, 1989

Genomics, cys-loop ligand-gated ion channels and new targets for the control of insect pests and vectors. Current Opinion in Insect Science 30: 1-7, 2018