Dihydrooxadiazines: Octopaminergic system as a potential site of insecticidal action

Dihydrooxadiazines are structural analogs of octopamine and were compared with octopamine for their ability to compete with [³H]dihydroergocryptine ([³H]DHE) for binding sites on DHE-sensitive receptors, to stimulate adenylate cyclase activity in nervous system homogenates of Periplaneta americana L., and to modulate the action of the peptide proctolin on the oviducal muscles of Locusta migratoria L. [³H]DHE binding was inhibited by low concentrations (μM range) of octopamine, phentolamine, N-demethylchlordimeform (DCDM) and several dihydrooxadiazines. The tested dihydrooxadiazines acted as aminergic agonists in stimulating cyclic AMP production in cockroach nervous system homogenates and did not show additive effects with octopamine, whereas additivity was observed with 5-hydroxytryptamine. The relative potency of octopaminergic antagonists, including mianserin, cyproheptadine, phentolamine, and gramine, to block octopamine-mediated elevation of cyclic AMP production was similar to the rank-order potency of the same antagonists to inhibit dihydrooxadiazine-mediated elevation of cyclic AMP production. Octopamine, 2-(4-bromophenyl)-5,6-dihydro-4H-1,3,4-oxadiazine (4-Br-PDHO), and 8-Br-cyclic AMP caused increased phosphorylation of proteins that are phosphorylated by exogenously added cyclic AMP-dependent protein kinase. These results indicate that the dihydrooxadiazine-induced rise in cyclic AMP levels in homogenates of the cockroach nervous system results directly in activation of an endogenous cyclic AMP-dependent protein kinase. 4-Br-PDHO behaved similarly to octopamine in modulating the action of proctolin-induced contractions in locust oviducal muscles. These observations suggest that dihydrooxadiazines act as octopamine agonists and have an octopaminergic action in modulating the action of proctolin. Thus, it is proposed that dihydrooxadiazines exert at least part of their insecticidal and miticidal actions through interaction with the octopaminergic system.     

Toxicodynamics of malaoxon in house flies

The fate of malaoxon was studied in a susceptible and a resistant strain of house fly following topical application. Sublethal doses were used: 160 pmol for the S-strain (0.17 × LD₅₀) and 1570 pmol for the R-strain (0.1 × LD₅₀). The penetration rates are dose dependent and semilog plots of the external amount vs time show that these rates are not proportional to this external amount. Internal concentrations of malaoxon rapidly increase following administration, reach maximum values between 30 min and 2 hr (depending on dose), and then slowly decrease. The rate of metabolic degradation is highest in the early stage of the intoxication process. A three-compartment pharmacokinetic model is postulated to explain the experimental data quantitatively. The first compartment represents external malaoxon, the other two represent internal parent compound. Statistical analysis shows that the penetration rate is better described with a sum of two exponentials rather than with a single exponential decay. In the model, degradation occurs in the first internal compartment and is assumed to be first order. Malaoxon is distributed between the two internal compartments slowly with first-order kinetics. Parameter estimation with curve-fitting procedures for the internal processes (degradation and exchange) shows that there is not one set of parameter values that can be used for both strains simultaneously. This prompted a study of possible interstrain differences in degradation capacities. It was found that in vitro the R-strain had a fourfold higher oxidative breakdown rate of malaoxon. Taking this difference into account it is possible to explain the two sets of data with one kinetic model, although other alternatives cannot be excluded.     

The insecticidal action of some components of wood preservatives

The use of liquid insecticide formulations for prevention and eradication of attack by common wood-boring insects is discussed and some methods of testing and assessing effectiveness described. Gamma-BHC and dieldrin prevent attack when present at 20 g/m³ of softwood while a number of stomach poisons are effective at from 1 to 10 kg/m³. The important part played by the organic solvent in an eradicant formulation is considered. Anobium punctatum in confined spaces can also be controlled by annual use of plastic strips emitting dichlorvos vapour. At 0.015 to 0.05 μg/l in air, dichlorvos virtually prevents initiation or spread of attack by this insect.     

Mode of action of insecticidal dihydropyrazoles: Selective block of impulse generation in sensory nerves

When injected into cockroaches (Periplaneta americana), dihydropyrazoles (pyrazolines), e.g. RH 3421, methyl 1-(N-(α,α,α-trifluoro-p-tolyl)carbamoyl-3-(4-chlorophenyl)-4-methyl-2-pyrazolin-4-ylcarboxylate, caused incoordination, followed by prostration and violent tremors. After several hours, prostrate cockroaches became very still, appearing paralyzed, but for several days they retained the ability to produce violent tremors when physically disturbed. The paralysis was associated with block of spontaneous activity in sensory nerves of cockroaches, tobacco hornworm larvae (Manduca sexta) and housefly larvae (Musca domestica). Block of spontaneous central nervous system activity was also seen in some cases. Current-clamp experiments on the cell body of the crayfish slowly-adapting stretch receptor neuron revealed that spike initiation in response to injected current was blocked by dihydropyrazoles, with no change in resting potential or input resistance, suggesting that the sodium current was suppressed. Hyperpolarization of blocked stretch receptors could reverse block, and crayfish giant axons, which were not normally sensitive to block by dihydropyrazoles, were rendered sensitive when artificially depolarized by elevation of extracellular potassium ion concentration, leading to the conclusion that the block of sodium current was strongly voltage dependent. The proposed mode of action, while similar to that of local anesthetics, class I anticonvulsants and class I antiarrhythmics, is novel for an insecticide.     

Synthesis,insecticidal activity and pyrethroidal mode of action of new tin ether derivatives

A novel range of trimethylstanniomethyl ethers of well known pyrethroid alcohols were synthesised, and their insecticidal activities and modes of action as insecticides were investigated. Among them, ethers from three types of alcohol (3-phenoxybenzyl, 4-fluoro-3-phenoxybenzyl and 6-phenoxy-2-pyridylmethyl) showed remarkable insecticidal activities against rice stem borers, houseflies and German cockroaches. According to electrophysiological studies on the abdominal nerve cords of German cockroaches, trimethylstanniomethyl 6-phenoxy-2-pyridylmethyl ether induced a rapid decline in spontaneous firing similar to that from tetramethrin. However, insecticidal trimethyltin chloride caused an entirely different response. These observations suggest that the present tin ether derivatives resemble pyrethroids, rather than the insecticidal tin compounds known so far.     

Novel mode of action of spinosad: Receptor binding studies demonstrating lack of interaction with known insecticidal target sites

The ability of spinosyn A to either enhance or displace binding to selected insecticidally-relevant receptors was investigated using a number of radioligands including, [³H]imidacloprid and [³H]ivermectin in tissues from the ventral nerve cord (VNC) membranes of the American cockroach, Periplaneta americana and head membranes from the housefly, Musca domestica. In these insect neural tissues, spinosyn A does not appear to alter the binding of a number of radioligands suggesting that spinosyn A does not interact directly with a variety of known receptors, including nicotinic or γ-aminobutyric acid (GABA)-based insecticidal target sites. However, available data are consistent with spinosyn A interacting with a site distinct from currently known insecticidal target sites, thus supporting a novel insecticidal mechanism of action for the spinosyns.     

An introduction to the principles of neurophysiology

Several of the research papers in this Symposium will refer to physiological processes with which most non-biologist readers are unfamiliar. The aim of this introductory paper, therefore, is to give those people a broad introduction to the basic principles of nerve and muscle physiology.     

Bacillus thuringiensis vegetative insecticidal protein family Vip3A and mode of action against pest Lepidoptera

Vip3A proteins are widely used for controlling pest Lepidoptera. Different binding sites with different receptors in the insect midgut membrane and lack of cross‐resistance with crystal (Cry) proteins enhance their applicability, as both single proteins and proteins pyramided with Cry proteins in transgenic Bt crops. Vip3A proteins are effective but there is relatively little information about their structure, function, activation, specificity, and mode of action. In addition, the mechanism of insect resistance to these proteins is unknown. Phylogenetic analysis and multiple sequence alignment showed that Vip3A proteins are genetically distant from Cry proteins. The mode of action and insecticidal activity of Vip3A proteins are discussed in this review. This review also provides detailed information about the Vip3A protein family that may aid in the design of more efficient pest management strategies in response to insect resistance to insecticidal proteins. © 2020 Society of Chemical Industry     

Synergistic effects of agonists and antagonists in insect venoms—a natural way of insecticidal action

Contrary to the typical killing action of most animal venoms, including social wasp venoms, the solitary wasp venoms seem to have been created to paralyse the prey. This suggests a specific action on parts of the nervous system. However, the solitary wasp venoms studied, contain many agonists and antagonists of synaptic transmission, and their paralysing action is very complicated. Besides a contribution of agonists to initiate and enhance the action of antagonists, one of the venoms contains two antagonists with different actions, and one of these antagonists enhances the effect of the other. The specific action of both toxins and their interaction will be discussed as an example of how nature enhances pesticide action through mixtures.     

杀虫活性多肽研究进展

传统杀虫剂在防治害虫、保障农作物丰收等方面做出了卓越贡献,但是由于其化学性质以及不合理使用,对环境也带来了一些负面影响。因此,以环境友好为前提,寻找结构独特、性能优异以及绿色安全的杀虫剂尤为迫切。多肽是由多个氨基酸通过肽键连接而成,也是蛋白质降解而成的中间产物,在生命过程中具有重要作用。近年来,杀虫活性多肽因其新颖的作用机制、优异的活性、理想的环境相容性而成为农药领域一颗冉冉升起的新星。本文主要从来源于动物、植物和微生物的杀虫活性多肽角度出发,综述了其近年来的研究进展及应用,并对未来的研究趋势进行了展望。     

Spray impaction,retention and adhesion: An introduction to basic characteristics

Droplets, falling under gravity through air that is not moving relative to the target, will impact on any object in their path, while charged droplets will be drawn to objects of earth potential along paths normal to the lines of equipotential; thus near the catching surface, they will move directly towards it. If the air is moving relative to the target, it will tend to move the droplets with it. The greater the drag to mass ratio of a droplet, the more rapidly any initial motion it has through the air will cease, and it will move through the air only very slowly under the effects of gravity and any electromagnetic potential. Air flowing past an object is able to change its path rapidly, but droplets moving with the air are less able to do this. Their ability to avoid impact increases with decrease in droplet size and wind speed, and with increase in the size of the catching surface. Thus small smooth stems catch big droplets in a high wind efficiently, but large smooth branches in a light wind will not catch many small droplets. Artificial cylinders and ribbons are poorer at catching droplets than natural surfaces, which are rarely smooth and often hairy. Hairs or spikes on a surface greatly increase the catch efficiency of droplets carried in the wind. A droplet several hundred micrometres in diameter is so dominated by gravity that it will fall in a near vertical path even in a moderate wind, impacting on any horizontal surface that obstructs its path. Its chances of reaching a vertical stem are negligible unless it runs off or splashes from a near horizontal surface. Conversely, a small droplet will be carried almost horizontally in any wind and is most likely to impact on vertical surfaces or flapping leaves. It has a much greater chance of getting inside the canopy without being caught because most leaves are near horizontal, and once there, it must rely on the turbulence induced by the wind for transport and impaction on undersurfaces or hairs. Because turbulence is reduced as the droplet nears the ground, it is very difficult to catch droplets on the lower parts of the crop within the canopy. To bounce, a droplet must have enough surplus kinetic energy to rebound clear of the surface, allowing for the energy losses in deforming the droplet in the bounce process; moreover, the surface must not be significantly wetted by the drop. Thus the droplet must be moderate to large in size, must be moving rapidly relative to the surface, and must have a high surface tension to contain it as a droplet, even at its extreme deformation. Surface condition is of great importance; the presence of hairs and the type of roughness affect the probability of maintaining an air film between the surface and the droplet. In general, droplets below 150 μm diameter are unlikely to bounce, but adding small amounts of surfactant to the droplet formulation can increase this size by several times. Any one plant leaf can vary considerably over its area because of age, abrasion and local surface shape. A film of water on a wet surface ensures an air film is maintained and the droplet will bounce.     

一种新型的简易展翅板

本文介绍了一种美观、实用、新型展翅板的制作方法及其基本性能。这一新型展翅板较通用展翅板制作方便，较市面上的展翅板更为经济实惠。     

Quantitative structure-activity relationships of insecticidal diphenyldichlorocyclopropanes

Neurophysiological activity of a series of aromatic-substituted 1,1-diphenyl-2,2-dichlorocyclopropanes (DCC analogs) in the induction of repetitive discharges in excised central nerve cords of the American cockroach was determined by an extracellular recording technique. Quantitative analysis using physicochemical parameters showed that variations in the activity were parabolically correlated with the van der Waals volume of aromatic substituents. Insecticidal activity of these compounds in the American cockroach under conditions where oxidative metabolic activity was inhibited by piperonyl butoxide was also determined. This was related to the repetitive nerve discharge activity, when transport factors were separated by using a hydrophobicity parameter. The analyses showed that the aromatic substituent effects on the neurophysiological activity as well as the relationship between insecticidal and neurophysiological activities are very close to those observed previously for DDT analogs including DDT, DDD, and prolan derivatives.     

二氢吡唑邻甲酰氨基苯甲酰胺衍生物的合成及杀虫活性

以邻氨基苯甲酸和4,5-二氢吡唑-5-甲酸为原料,制备得到苯并噁嗪酮,所得产物与取代胺作用制得8个结构新颖的二氢吡唑邻甲酰胺基苯甲酰胺类化合物,其结构用核磁共振氢谱和质谱进行了表征。生物活性试验结果表明,在500 mg/L质量浓度下,部分化合物对小菜蛾Plutella xylostella、苜蓿蚜Aphis medicaginis和稻飞虱Nilaparvata lugens的致死率达100%。     

Engineering of Bacillus thuringiensis insecticidal proteins

Bacillus thuringiensis (Bt) has been used as sprayable pesticides for many decades. Bt strains utilized in these products produce multiple insecticidal proteins to complement a narrow insect specificity of each protein. In the late 1990s, genes encoding Bt insecticidal proteins were expressed in crop plants such as cotton and corn to protect these crops from insect damage. The first Bt protein used in transgenic cotton was Cry1Ac to control Heliothis virescens (tobacco budworm). Cry1Ab was applied to corn to control Ostrinia nubilalis (European corn borer). Since these insects have developed resistance to Cry1Ac and Cry1Ab, new Bt proteins are required to overcome the resistance. In order to protect corn furthermore, it is desired to control Diabrotica virgifera (Western corn rootworm), Helicoverpa zea (corn earworm) and Spodoptera frugiperda (fall armyworm). Recently, many new Bt insecticidal proteins have been discovered, but most of them require protein engineering to meet the high activity standard for commercialization. The engineering process for higher activity necessary for Bt crops is called optimization. The seed industry has been optimizing Bt insecticidal proteins to improve their insecticidal activity. In this review, several optimization projects, which have led to substantial activity increases of Bt insecticidal proteins, are described.     

Glucosinolate aglucones and analogues: insecticidal properties and a QSAR

Naturally occurring aglucones of three glucosinolates (sinigrin, glucotropaeolin, and epi-progoitrin) were tested for fumigation activity against the house fly, Musca domestica, and the lesser grain borer, Rhizopertha dominica. A total of eight natural aglucones were evaluated in the bioassays. Two aglucones of sinigrin showed efficacy against both species which was comparable with that of a commercial fumigant, chloropicrin. None of the aglucones tested was comparable in activity to dichlorvos. Aglucones of glucotropaeolin were also insecticidal, but not to the same level as the sinigrin aglucones. The aglucones of epi-progoitrin were only slightly effective as fumigants. A quantitative structure–activity relationship (QSAR) was developed for synthetic analogues of the sinigrin and glucotropaeolin aglucones. An electronic parameter, σ*, provided the best predictor of activity in R. dominica, whereas a hydrophobicity parameter, π, best predicted activity in M. domestica. © 1998 Society of Chemical Industry