Abstract:Mosquito-vectored disease remains a significant global public health threat. One of the most significant barriers to mosquito control is the evolution of insecticide resistance and limited number of available insecticide classes. Isoxazolines and meta-diamides are two classes of insecticides targeting the gamma-aminobutyric acid (GABA) channel, a target site currently under-utilized in mosquito adulticides. Topical assays were conducted on laboratory colonies of the yellow fever mosquito, Aedes aegypti L. (Diptera: Culicidae), and the common malaria mosquito, Anopheles quadrimaculatus Say (Diptera: Culicidae), with three isoxazolines: afoxolaner, fluralaner, and fluxametamide, the meta-diamide, broflanilide, and the pyrethroid deltamethrin, a commonly used and well-studied insecticide for adult mosquito control. The insecticides were tested against susceptible and pyrethroid resistant Ae. aegypti and susceptible An. quadrimaculatus. Broflanilide and afoxolaner were found to be the most and least toxic, respectively, and all five compounds were more toxic to Ae. aegypti than An. quadrimaculatus. Cross-resistance to afoxolaner, fluralaner, and fluxametamide, and broflanilide was low or not found in the pyrethroid resistant CKR strain. Age ratios were low to insignificant, suggesting no difference in toxicity between younger and older mosquitoes. While not as toxic as deltamethrin, the isoxazolines and meta-diamide, broflanilide, represent promising classes of insecticides that could be formulated for use against adult mosquitoes, with the advantages of a favorable mammalian toxicological profile and no cross-resistance in pyrethroid resistant strains.