ArticlePLoS pathogens2021
The molecular targets of ivermectin and lotilaner in the human louse Pediculus humanus humanus: New prospects for the treatment of pediculosis.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 34 citations in OpenAlex.
- Pyridazine and pyridazinone compounds in crops protection: a review.Molecular diversity · 2025Review
- Molecular detection of novel Glutamate-gated chloride channel mutations in field collected human head lice (Phthiraptera: Pediculidae) from Iran.BMC research notes · 2025Article
- Identification and Spatiotemporal Expression of a Putative New GABA Receptor Subunit in the Human Body LouseGenes · 2024Article
- Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.Advances in parasitology · 2024Article
- Evaluation of the scabicidal effect of a single dose of fluralaner in a rabbit model of crusted scabies.Parasitology research · 2023Article
- Blood-feeding adaptations and virome assessment of the poultry red mite Dermanyssus gallinae guided by RNA-seq.Communications biology · 2023Article
- Pharmacokinetic and pharmacodynamic considerations for treating sarcoptic mange with cross-relevance to Australian wildlife.International journal for parasitology. Drugs and drug resistance · 2023Review
- Transcriptome of the synganglion in the tick Ixodes ricinus and evolution of the cys-loop ligand-gated ion channel family in ticks.BMC genomics · 2022Article
- Human pediculosis, a global public health problem.Infectious diseases of poverty · 2022Review
- Pharmacological characterization of novel heteromeric GluCl subtypes from Caenorhabditis elegans and parasitic nematodes.British journal of pharmacology · 2022Article
- Molecular and Functional Characterization of GABA Receptor Subunits GRD and LCCH3 from Human LouseMolecular pharmacology · 2021Article
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8 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Control of infestation by cosmopolitan lice (Pediculus humanus) is increasingly difficult due to the transmission of parasites resistant to pediculicides. However, since the targets for pediculicides have no been identified in human lice so far, their mechanisms of action remain largely unknown. The macrocyclic lactone ivermectin is active against a broad range of insects including human lice. Isoxazolines are a new chemical class exhibiting a strong insecticidal potential. They preferentially act on the γ-aminobutyric acid (GABA) receptor made of the resistant to dieldrin (RDL) subunit and, to a lesser extent on glutamate-gated chloride channels (GluCls) in some species. Here, we addressed the pediculicidal potential of isoxazolines and deciphered the molecular targets of ivermectin and the ectoparasiticide lotilaner in the human body louse species Pediculus humanus humanus. Using toxicity bioassays, we showed that fipronil, ivermectin and lotilaner are efficient pediculicides on adult lice. The RDL (Phh-RDL) and GluCl (Phh-GluCl) subunits were cloned and characterized by two-electrode voltage clamp electrophysiology in Xenopus laevis oocytes. Phh-RDL and Phh-GluCl formed functional homomeric receptors respectively gated by GABA and L-glutamate with EC50 values of 16.0 μM and 9.3 μM. Importantly, ivermectin displayed a super agonist action on Phh-GluCl, whereas Phh-RDL receptors were weakly affected. Reversally, lotilaner strongly inhibited the GABA-evoked currents in Phh-RDL with an IC50 value of 40.7 nM, whereas it had no effect on Phh-GluCl. We report here for the first time the insecticidal activity of isoxazolines on human ectoparasites and reveal the mode of action of ivermectin and lotilaner on GluCl and RDL channels from human lice. These results emphasize an expected extension of the use of the isoxazoline drug class as new pediculicidal agents to tackle resistant-louse infestations in humans.
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