title: Development of a mouse model to determine the systemic activity of potential flea-control compounds.
abstract: Probe studies were performed to determine if the cat flea (Ctenocephalides felis), the most common ectoparasite of companion animals, will feed on laboratory mice and, if so, to incorporate this into a small animal assay to detect systemically active compounds. Consequently, a protocol was developed which incorporated acepromazine maleate to temporarily sedate various strains of mice and allow fleas a window of time to feed undisturbed. For validation of the model, CD-1 mice were dosed per os with seven known insecticides at 30, 10 and 1mg/kg. Mice were sedated with 0.0125 ml acepromazine maleate intraperitoneally, and infested with fleas. After 2h, fleas were removed, one-third were examined immediately to confirm the occurrence of feeding, and 77% were found to have ingested a blood meal. The remaining fleas were incubated for 24h to determine mortality. Nitenpyram, the active ingredient in Capstar, was highly active (>94%) at 1mg/kg. Selamectin, the active ingredient in Revolution, was very active (86%) at 10mg/kg, but inactive at 1mg/kg. Fipronil, the active ingredient of Frontline Topspot, was very active (83%) at 30 mg/kg, moderately active (54%) at 10mg/kg and inactive at 1mg/kg. Cythioate, the active ingredient in Proban, and nodulisporic acid, a recently discovered oral insecticide, were moderately active (64 and 55%, respectively) at 10mg/kg, but both were inactive at 1mg/kg. Lufenuron and ivermectin exhibited no efficacy at any level tested. These findings suggest that this mouse model can effectively identify systemic flea-control leads and, subsequently, reduce the use of large animals in research.
authors.affiliation: Merck Research Labs, Merck & Co., Inc., P.O. Box 2000, Rahway, NJ 07065, USA. karen_santora@merck.com
authors.forename: Karen A
authors.initials: KA
authors.lastname: Santora
authors.forename: Michelle
authors.initials: M
authors.lastname: Zakson-Aiken
authors.forename: Cordelia
authors.initials: C
authors.lastname: Rasa
authors.forename: Wes
authors.initials: W
authors.lastname: Shoop
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology*; D002371:Cat Diseases / Q000517:prevention & control*; D002415:Cats; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004478:Ectoparasitic Infestations / Q000517:prevention & control / Q000662:veterinary*; D007300:Insect Control / Q000379:methods; D007306:Insecticides / Q000494:pharmacology*; D051379:Mice; D021261:Parasitic Sensitivity Tests / Q000662:veterinary; D005423:Siphonaptera / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000977:Antiparasitic Agents; D007306:Insecticides