Studies on the mode of action of spinosad: The internal effective concentration and the concentration dependence of neural excitation

This is the second in a series of reports that define the mode of action of spinosyns, a novel class of naturally derived insecticidal macrocyclic lactones. The concentration dependence of central nervous system (CNS) stimulation was determined using ganglia isolated from cockroaches, house fly larvae, and tobacco hornworm larvae. The tobacco hornworm nervous system was most sensitive, with a steep dose-response relation and an ED(50) of 5 nM for spinosyn A. The response of the housefly CNS was comparable, showing no clear effect at 3 nM and near-maximal stimulation at 10 nM spinosyn A. The cockroach CNS also displayed a steep dose-response relation, with a threshold of 10 nM and an EC(50) of 32 nM. That the nerve cords of cockroaches are exposed to comparable levels of spinosyn A during poisoning was established by comparison of the concentration of spinosyn A taken up by cockroach nerve cords during exposure in vivo, in cockroaches treated with a threshold dose, with that in isolated nerve cords equilibrated with a solution of spinosyn A in saline. A saline concentration of 21 nM was estimated to give the same nerve cord reaches a concentration inside the insect that is sufficient to directly excite the central nervous system. (C)1998 Academic Press.