ArticleParasites & vectors2025
Comparative analysis of isoxazoline activity on human and canine GABA receptors expressed in Xenopus oocytes.
Article in Parasites & vectors, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIsoxazolines, including sarolaner, lotilaner, afoxolaner and fluralaner, are a class of ectoparasiticides that target gamma-aminobutyric acid receptors (GABARs) in insects and acari. However, their potential action on mammalian GABARs has not been extensively compared.
methodsThis study investigated the inhibitory effects of these isoxazolines on human and canine GABARs expressed in Xenopus oocytes. Eleven functional GABAR subunit combinations from human and canine isoforms were successfully cloned and expressed. Two-electrode voltage-clamp measurements were performed to determine the inhibitory effects of the isoxazolines.
resultsSarolaner, afoxolaner and fluralaner exhibited partial to high inhibition of human and canine GABARs, with fluralaner showing the lowest half-maximal inhibitory concentration (IC
conclusionsWhile neurological adverse events have been reported in dogs, particularly in breeds with the multidrug resistance 1 (MDR1) gene mutation, this study suggests that direct inhibition of canine GABARs may not be the primary cause. However, the interpretation of these results represents a challenge, and a direct correlation with documented cases of adverse events remains difficult. Further research is needed to understand the exposure of mammalian GABARs to isoxazolines and the analog-specific safety risks associated with the observed in vitro receptor activities.
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