The mode of action of spinosoid insecticides is by a neural mechanism. The spinosyns and spinosoids have a novel mode of action, primarily targeting binding sites on nicotinic acetylcholine receptors (nAChRs) of the insect nervous system that are distinct from those at which other insecticides have their activity. Spinosoid binding leads to disruption of acetylcholine neurotransmission. Spinosad also has secondary effects as a γ-amino-butyric acid (GABA) neurotransmitter agonist. It kills insects by hyperexcitation of the insect nervous system. Spinosad so far has proven not to cause cross-resistance to any other known insecticide. Use
Spinosad has been used around the world for the control of a variety of insect pests, including Lepidoptera, Diptera, Thysanoptera, Coleoptera, Orthoptera, and Hymenoptera, and many others. It was first registered as a pesticide in the United States for use on crops in 1997. Its labeled use rate is set at 1 ppm (1 mg a.i./kg of grain) and its maximum residue limit (MRL) or tolerance is set at 1.5 ppm. Spinosads widespread commercial launch was deferred, awaiting final MRL or tolerance approvals in a few remaining grain-importing countries. It is considered a natural product, thus is approved for use in organic agriculture by numerous nations. Two other uses for spinosad are for pets and humans. Spinosad has recently been used in oral preparations (as Comfortis) to treat C. felis, the cat flea, in canines and felines; the optimal dose set for canines is reported to be 30 mg/kg.Spinosad is sold under the trade names, Comfortis, Trifexis, and Natroba. Trifexis also includes milbemycin oxime.
Comfortis and Trifexis brands treat adult fleas on pets; the latter also prevents heartworm disease. Natroba is sold for treatment of human head lice. Spinosad is also commonly used to kill thrips. Spinosyn A
Spinosyn A does not appear to interact directly with known insecticidal-relevant target sites, but rather acts via a novel mechanism. Spinosyn A resembles a GABA antagonist and is comparable to the effect of avermectin on insect neurons. Spinosyn A is highly active against neonate larvae of the tobacco budworm, Heliothis virescens, and is slightly more biologically active than spinosyn D. In general, spinosyns possessing a methyl group at C6 (spinosyn D-related analogs) tend to be more active and less affected by changes in the rest of the molecule. Spinosyn A is slow to penetrate to the internal fluids of larvae; it is also poorly metabolized once it enters the insect. The apparent lack of spinosyn A metabolism may contribute to its high level of activity, and may compensate for the slow rate of penetration. Resistance
Spinosad resistance has been found in Musca domestica by Liu & Yue 2000, in Plutella xylostella by Sayyed et al 2004, in Bactrocera dorsalis by Hsu & Feng 2006, in Frankliniella occidentalis by Bielza et al 2007, and in Cydia pomonella by Reyes et al 2007; see Insecticide Resistance Action Committees Arthropod Pesticide Resistance Database for continued updates.