New GABA/Glutamate Receptor Target for [3H]Isoxazoline Insecticide

The highly effective and selective isoxazoline insecticide A1443 is known to potently displace [H-3]ethynylbicycloorthobenzoate ([H-3]EBOB) binding to house fly head membranes with an IC50 of 0.2 nM in a manner characteristic of GABA-gated chloride channel antagonists. To further define its mode of action, we prepared phenyl-labeled [H-3]A1443 as described with a specific activity of 14 Ci/mmol. This new radioligand with an apparent IC50 of about 0.4 nM is poorly displaced by most insecticides acting at the [H-3]EBOB site. Interestingly, the isoxazoline binding site is directly coupled to the avermectin GABA/glutamate chloride channel activator site. These findings revive interest in the insect GABA/glutamate receptor as an insecticide target.