Diamide insecticide target site specificity in the Heliothis and Musca ryanodine receptors relative to toxicity.

Anthranilic and phthalic diamides act on the ryanodine receptor (RyR), which constitutes the Ca2+-activated Ca2+ channel and can be assayed as shown here in Heliothis thoracic muscle tissue with anthranilic diamide [3H]chlorantraniliprole ([3H]Chlo), phthalic diamide [3H]flubendiamide ([3H]Flu), and [3H]ryanodine ([3H]Ry). Using Heliothis with [3H]Chlo or [3H]Flu gives very similar anthranilic and phthalic diamide binding site structure–activity correlations, indicating a common binding site. The anthranilic and phthalic diamide stimulation of [3H]Ry binding in Heliothis generally parallels their inhibition of [3H]Chlo and [3H]Flu binding. In Musca adults [3H]Ry binding site stimulation is a good predictor of in vivo activity for anthranilic but not phthalic diamides, and no high-affinity [3H]Flu specific binding site is observed. These relationships establish species differences in diamide target site specificity important in structure optimization and target site-based resistance mechanisms.