Mesoionic insecticides: a novel class of insecticides that modulate nicotinic acetylcholine receptors.

BACKGROUND: As the world population grows towards 9 billion by 2050, it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields owing to pests. The development of new insecticides will help to sustain this protection and overcome insecticide resistance. RESULTS: A novel class of mesoionic compounds has been discovered, with exceptional insecticidal activity on a range of Hemiptera and Lepidoptera. These compounds bind to the orthosteric site of the nicotinic acetylcholine receptor and result in a highly potent inhibitory action at the receptor with minimal agonism. The synthesis, biological activity, optimization and mode of action will be discussed. CONCLUSION: Triflumezopyrim insect control will provide a powerful tool for control of hopper species in rice throughout Asia. Dicloromezotiaz can provide a useful control tool for lepidopteran pests, with an underexploited mode of action among these pests. © 2016 Society of Chemical Industry.

Movement of cyantraniliprole in plants after foliar applications and its impact on the control of sucking and chewing insects.

BACKGROUND: Given the physical properties of insecticides, there is often some movement of these compounds within crop plants following foliar application. In this context, movement of two formulations of cyantraniliprole, an anthranilic diamide, was characterized for translocation to new growth, distribution within a leaf and penetration through the leaf cuticle. RESULTS: Upward movement of cyantraniliprole to new plant growth via the xylem was confirmed using (14) C-radiolabeled cyantraniliprole and from Helicoverpa zea mortality on tomato leaves that had not been directly treated. Within a leaf there was significant acropetal movement (base to apex) of cyantraniliprole, but no significant basipetal movement (apex to base). Translaminar movement, the ability of a compound to penetrate the leaf cuticle, was demonstrated in a variety of plants, both with and without the use of adjuvants, by treating only the adaxial surface of the leaf and measuring control of diamondback moth (Plutella xylostella), green peach aphid (Myzus persicae) and sweetpotato whitefly (Bemisia tabaci) exposed in clip cages to the untreated abaxial surface. CONCLUSION: The plant mobility and plant protection of cyantraniliprole is discussed with implications for use in insect resistance management and integrated pest management programs.

Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs.

Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1-0.2 µg/ml to be effective against both fleas (Ctenocephalides felis) and ticks (Dermacentor variabilis). Pharmacokinetic profiles in dogs following a 2.5mg/kg oral dosage demonstrated uniform and predictable afoxolaner plasma concentrations above threshold levels required for efficacy for more than one month. Dose ranging and a 5-month multi-dose experimental study in dogs, established that the 2.5mg/kg oral dosage was highly effective against fleas and ticks, and produced predictable and reproducible pharmacokinetics following repeated dosing. Mode of action studies showed that afoxolaner blocked native and expressed insect GABA-gated chloride channels with nanomolar potency. Afoxolaner has comparable potency between wild type channels and channels possessing the A302S (resistance-to-dieldrin) mutation. Lack of cyclodiene cross-resistance for afoxolaner was confirmed in comparative Drosophila toxicity studies, and it is concluded that afoxolaner blocked GABA-gated chloride channels via a site distinct from the cyclodienes.