RESEARCH ARTICLE Dopamine Receptor Antagonists as New Mode-of-Action Insecticide Leads for Control of Aedes and CulexMosquito Vectors

Background New mode-of-action insecticides are sought to provide continued control of pesticide resis-tant arthropod vectors of neglected tropical diseases (NTDs). We previously identified an-tagonists of the AaDOP2 D1-like dopamine receptor (DAR) from the yellow fever mosquito, Aedes aegypti, with toxicity to Ae. aegypti larvae as leads for novel insecticides. To extend DAR-based insecticide discovery, we evaluated the molecular and pharmacological char-acteristics of an orthologous DAR target, CqDOP2, from Culex quinquefasciatus, the vector of lymphatic filariasis and West Nile virus. Methods/Results CqDOP2 has 94.7 % amino acid identity to AaDOP2 and 28.3 % identity to the human D1-like DAR, hD1. CqDOP2 and AaDOP2 exhibited similar pharmacological responses to bio-genic amines and DAR antagonists in cell-based assays. The antagonists amitriptyline, amperozide, asenapine, chlorpromazine and doxepin were between 35 to 227-fold more selective at inhibiting the response of CqDOP2 and AaDOP2 in comparison to hD1. Antago