Pharmaceutical technologies with potential application to insecticide discovery†.

Novel neuroactive insecticides are discovered/registered differently, have a lower value in use, and exert their physiological actions in manners distinct from neuroactive pharmaceuticals, but there are clear similarities in their biochemical modes of action. Insecticides are generally discovered using whole pest insect screens, and this eases difficulties in 'translational science' from laboratory to field, as opposed to pharmaceutical translation from biochemical or cell-based targets to animal models to human clinical trials to registered drug. This paper examines recent trends in pharmaceutical science and identifies some technologies which may represent complementary approaches to insecticide discovery screening and mode of action determination beyond the sound processes in common practice today. Examples will be drawn from nanoparticle delivery of neuroactives, unique ligand-polymer conjugates, proposed advances in insect cell culture following from pharmaceutical cell biology, and laboratory or organ-on-a-chip approaches. It is hoped that these concepts will stimulate novel thinking which may enable discovery of efficacious new neuroactive insecticides. © 2020 Society of Chemical Industry.

It takes a team: reflections on insecticide discoveries, toxicological problems and enjoying the unexpected.

Absorption/distribution/metabolism/excretion (ADME)-related studies are mandatory in agrochemical development/registration, but can also play a valuable role in the discovery process. In combination with target-site potency, bioavailability/ADME characteristics determine agrochemical bioactivity and selectivity, and these concerns can dictate the fate of a discovery lead area. Bioavailability/ADME research was critical to the eventual commercialization of three different insecticide chemistries examined in this paper. In one situation, improved systemicity in anthranilic diamides was required to expand pest spectrum. In another, ADME tools were needed to improve the selective toxicity and non-target safety of sodium channel blocker insecticides. Finally, differential ADME characteristics of two classes of hormone agonists dictated differential insecticidal activity, and were useful in optimizing the dibenzoylhydrazine ecdysone agonists. ADME discovery research will help companies to advance novel, efficacious and selective agrochemicals, but organizational patience and a desire to understand lead areas in depth are required. © 2016 Society of Chemical Industry.

Toxicity of a formulation of the insecticide indoxacarb to the tarnished plant bug, Lygus lineolaris (Hemiptera: Miridae), and the big-eyed bug, Geocoris punctipes (Hemiptera: Lygaeidae).

Indoxacarb is a new oxadiazine insecticide that has shown outstanding field insecticidal activity. The toxicity of a 145 g litre-1 indoxacarb SC formulation (Steward) was studied on the tarnished plant bug Lygus lineolaris and the big-eyed bug Geocoris punctipes. Both insect species responded very similarly to indoxacarb in topical, tarsal contact and plant feeding toxicity studies. The topical LD50 of the formulation was c 35 ng AI per insect for both species. Prolonged tarsal contact with dry indoxacarb residues did not result in mortality for either insect species. However, both species were susceptible to feeding through dried residues of indoxacarb after spraying on young cotton plants. Feeding on water-washed plants resulted in lower mortality than that observed with unwashed plants, and toxicity declined even more dramatically after a, detergent rinse, indicating that much of the indoxacarb probably resides on the cotton leaf surface or in the waxy cuticle. These results were corroborated by HPLC-mass spectrometry measurements of indoxacarb residues on the plants. Greater mortality for both species was observed in a higher relative humidity environment. Higher levels of accumulated indoxacarb and its active metabolite were detected in dead G punctipes than in L lineolaris after feeding on sprayed, unwashed plants. When female G punctipes ate indoxacarb-treated Heliothis zea eggs, there was significant toxicity. However, only c 15% of the females consumed indoxacarb-treated eggs, and the rest of the females showed a significant diminution of feeding in response to the insecticide. Cotton field studies have shown that indoxacarb treatments at labelled rates lead to a dramatic decline in L lineolaris, with negligible declines in beneficial populations. A major route of intoxication of L lineolaris in indoxacarb-treated cotton fields thus appears to be via oral, and not cuticular, uptake of residues from treated cotton plants. The mechanisms for selectivity/safety for G punctipes are currently under investigation and may be a combination of differential feeding behavior and diminution of feeding by females exposed to indoxacarb-treated eggs.