Studies on the mode of action of spinosad : Insect symptoms and physiological correlates

This is the first in a series of reports that define the novel mode of action of spinosyns, a new class of macrocyclic lactone natural products for insect control. Spinosyn A, the major active component of spinosad, was used as a model for these studies. Spinosyn A initially caused involuntary muscle contractions and tremors by widespread excitation of neurons in the central nervous system. Spinosyn A also caused excitation when applied directly to isolated insect ganglia at submicromolar concentrations. Prolonged spinosyn-induced hyperexcitation resulted in paralysis that was associated with neuromuscular fatigue. However, spinosyn A had no direct neuromuscular depressant effect and at very high concentrations actually enhanced neuromuscular transmission.