Multiple Sites of Insecticidal Action in Ionotropic GABA Receptors

Pentameric ligand-gated ion channels (LGICs) of insects are among the targets of existing insecticides. Given the presence of multiple ligand-binding sites and the allostery in LGICs, more studies could provide further opportunities for insecticide discovery. Ionotropic gamma-aminobutyric acid (GABA) receptors (GABARs) fall into the family of LGICs, and insect GABARs are insecticidal targets of fipronil, a conventional noncompetitive antagonist (cNCA), and of isoxazolines and benzamides, which are a novel type of NCAs and have a different site(s) of action from that of cNCAs. The mechanism of interaction of competitive antagonists with the orthosteric site merits further investigation for developing novel insecticidal compounds.