# Lotilaner is a potent inhibitor of the novel GABA receptor of body lice *Pediculus humanus humanus*

Nicolas Lamassiaude, Berthine Toubate, Cédric Neveu, Françoise

Debierre-Grockiego, Claude Charvet, Isabelle Dimier-Poisson

► To cite this version:

Nicolas Lamassiaude, Berthine Toubate, Cédric Neveu, Françoise Debierre-Grockiego, Claude Charvet, et al.. Lotilaner is a potent inhibitor of the novel GABA receptor of body lice *Pediculus humanus humanus*. 27. Conference of the World Association for the Advancement of Veterinary Parasitology, Jul 2019, Madison, United States. 349 p. *hal-02736610*

HAL Id: hal-02736610

https://hal.inrae.fr/hal-02736610

Submitted on 2 Jun 2020

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WAAVP

27th Conference of the World Association for
the Advancement of Veterinary Parasitology

JULY 7 - 11, 2019 | MADISON, WI, USA

Dedicated to the legacy of Professor Arlie C. Todd

Sifting and Winnowing the Evidence in Veterinary Parasitology

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@WAAVP2019

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@WAAVP_2019

Abstract Book

Joint meeting with the 64th American Association of Veterinary Parasitologists
Annual Meeting & the 63rd Annual Livestock Insect Workers Conference

www.WAAVP2019.com #WAAVP2019
the lesions. Twenty four hours after treatment all larvae were killed on all treated animals. Total amount of larvae recovered ranged from 3 to 327 larvae per animal (average of 67.7). Afoxolaner (NexGard®) at doses ranging from the minimum active dose of 2.5 mg/kg to the maximum dose 6.7 mg/kg (mean of 3.9 mg/kg) was rapidly efficacious for the treatment of 14 dogs with light, moderate and severe infestations with Cochliomyia hominivorax larvae, by eliminating all larvae within 24 hours after a single oral treatment.

## OA13.02 Lotilaner Is a Potent Inhibitor of the Novel GABA Receptor of Body Lice Pediculus Humanus Humanus

**Nicolas Lamassiaude**¹, Dr Berthine Toubate², Dr Pierre Charnet³, Dr Cédric Neveu¹, Dr Françoise Debière-Grockiego², Dr Claude Charvet¹, Pr Isabelle Dimier-Poisson²

¹ISP, INRA, Université Tours, UMR1282, Nouzilly, France, 2ISP, UFR de Pharmacie, Université Tours, UMR1282, Tours, France, ³Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Montpellier, France

Drug resistance in the parasites field, including the cosmopolitan lice (Pediculus humanus), and the prevalence increasing despite the marketing of new therapies are an important challenge for our societies. The major pharmacological targets of insecticides like pyrethrins, malathion, spinosad and ivermectin (also used as nematicide and acaricide) are the ligand gated ion channels present in the nervous system of insects. Currently, targets of these molecules remain largely unknown in body lice. Among those channels receptors, α-aminobutyric acid gated chloride ion channels (GABACl) are the main synaptic inhibitory receptors in insects, making them pertinent pharmacological targets.

In the present study, we identified and characterized the targets of insecticides in lice to decipher the mode of action of insecticides in Pediculidae. Research in the genomic databases of Pediculus humanus allowed us to identify a GABACl subunit encoded by the Resistance to dieldrin (Rdl) gene. We cloned the corresponding full-length cDNA into a transcription vector and performed in vitro

synthesis of the cRNAs, which were injected in the Xenopus oocysts system to reconstitute functional channels. Two-electrode voltage clamp recordings showed that Phh-RDL assemble into a homomeric receptor sensitive to different insecticides like fipronil, picrotoxin and lotilaner, a novel class of ectoparasiticide agent using to treat ticks and fleas of dogs (CredelioTM, Elanco). These results correlated with the efficacy of these drugs on lice in vivo. In conclusion, we report the functional characterization of the first GABACl of Pediculus humanus humanus. These results contribute to our understanding of the mode of action of insecticide compounds and will allow the development of new therapeutic strategies to control lice infestations.

## OA13.03 Early Oral Sarolaner (SimparicaTM, Zoetis) Acaricidal Activity Against Ixodes Scapularis and Amblyomma Americanum Adults After Monitored Attachment Intervals on Treated Dogs

**Dr. Kelly Allen**¹, Dr. Ruth Scimeca¹, Megan Wohltjen¹, Dr. Mason Reichard¹, Nadia Koziar², Deborah Amodie², Dr. Georgette Wilson², Dr. Joyce Login²

¹Oklahoma State University, Stillwater, United States, ²Zoetis Inc., Parsippany, United States

Acaricidal activity of oral sarolaner (SimparicaTM, Zoetis) against Rhipicephalus sanguineus sensu lato and Dermacentor reticulatus begins 4 and 8 hours, respectively, after induced infestations on treated dogs. Here, we evaluated Ixodes scapularis and Amblyomma americanum mortality in response to sarolaner after monitored, documented attachment time intervals within 1-8 hours of infestation. In duplicate, staggered infestation experiments, 6 treated and 6 control dogs were infested with 250 I. scapularis and 250 A. americanum adults. Ticks were allowed 60 minutes to embed mouthparts into the dermis. A ≤ 50% attachment rate was targeted. Subsets of ≤ 20 ticks were removed from dogs after documented attachment times of 1, 3, 5, and 7 hours or 2, 4, 6, and 8 hours. Live/dead status was assessed at the time of removal and 24 hours post-removal (live ticks incubated at ambient temperature (-70°F [21.1°C], 80-90%