Actions on insects

Thuringiensin (184), produced by B. thuringiensis (1,4) is a P-exotoxia that exerts its toxic action on insects and mammals through the inhibition of RNA polymerases. 

An alternative nomenclature (Type I and Type II) has been proposed for subgroups of pyrethroids based not only on the syndromes of intoxication produced in mammals but also on their chemical structures, their signs of poisoning in insects, and their actions on insect nerve preparations [2, 14, 18]. The Type I/II nomenclature has been used in parallel with the T/CS nomenclature, so that Type I and Type II pyrethroids are generally considered to induce T- or CS syndrome, respectively [4]. However, the relationship between the two syndromes and types are neither necessarily confirmed in all pyrethroids nor absolute from the recent available data. 

Another strategy of some interest is to deplete biogenic amines such as OA by inhibiting their biosynthesis. Inhibitors of such enzymes in the biosynthetic pathway as aromatic amino acid decarboxylase which converts tyrosine to tyramine, or dopamine 3 -hydroxylase which converts tyramine to OA are known and have interesting effects in insects (e.g. see 52,53)t but a discussion of this area lies outside the scope of this paper. Nevertheless, it is a particularly interesting one since these or related enzymes are also needed to produce catecholamines for cuticular sclerotiza-tion, thus offering dual routes to the discovery of compounds with selectively deleterious actions on insects. 

Lindane is the active y-isomer of hexachlorocyclohexane. It also exerts a neurotoxic action on insects (as well as humans). Irritation of skin or mucous membranes may occur after topical use. Lindane is active also against intrader-mal mites (Sarcoptes scabiei, causative agent of scabies), besides lice and fleas. It is more readily degraded than DDT. 

These inhibitors would be classified as anti-juvenile hormones and could be expected to show selective action on insects as a class. Such analogs are by no means just around the corner since at least two important properties that they should possess may be difficult to build into small organic molecules suitable for pest control. These properties are the ability to withstand general metabolic inactivation while retaining the ability to inhibit irreversibly the target enzymes of the corpus allatum and the property to accumulate selectively in corpora allata, a physically small target, so as to offset dilution in the general body cavity. 

Boric acid is an absorber of insect cuticle wax and a stomach poison. Its mode of action on insects has not been clearly established. Two major hypotheses have been proposed ... 

Buckingham SD, Lapied B, Le Corronc H, Grolleau E, and Sattelle DB (1997) Imidacloprid actions on insect neuronal acetylcholine receptors. The Journal of Experimental Biology 200 2685-2692. 

Ethyl-4-[2-(t-butylcarbonyloxy)butoxy] benzoate (ETB, ZR-2646, 71) occupies an intermediate position between the juvenile hormone mimics and the antijuvenile hormones to be discussed later. It acts as an anti-JH at low doses and as a JH mimic at high doses. The nature of this JH agonist/antagonist action is not understood, yet its interference with the induction of juvenile hormone esterase seems to elucidate at least partly its action on insects (Staal, 1977 Sparks et al., 1979). 

The relationship between the chemical structure and toxicity of various coumarin insecticides and anthelmintics are compiled (Table 3.13), and for comparison, some other related compounds are also tabulated. The mammalian toxicity of these compounds is moderate, and their selective action on insects is coimected with differences in metabolism. In mammals these chemicals are probably rapidly metabolised by hydrolysis between the aromatic and phosphate groups, whereas in insects by slow oxidation of the phosphorothionate to phos-... 

Mode of Action. All of the insecticidal carbamates are cholinergic, and poisoned insects and mammals exhibit violent convulsions and other neuromuscular disturbances. The insecticides are strong carbamylating inhibitors of acetylcholinesterase and may also have a direct action on the acetylcholine receptors because of their pronounced stmctural resemblance to acetylcholine. The overall mechanism for carbamate interaction with acetylcholinesterase is analogous to the normal three-step hydrolysis of acetylcholine however, is much slower than with the acetylated enzyme. 

Bates, Hewlett, and Lloyd (I) found that both piperonyl butoxide and SKF 525A, the ester of 2-diethylaminoethyl 2,2-diphenyl-w-pentanoate, synergized the action of pyrethrins on insects of species of the lesser mealworm beetles and houseflies but both antagonized the action of malathion. SKF 525A is known to increase the effects on mammals of drugs of various types and has been shown to synergize pyrethrins. 

Hurst (19) discusses the similarity in action of the pyrethrins and of DDT as indicated by a dispersant action on the lipids of insect cuticle and internal tissue. He has developed an elaborate theory of contact insecticidal action but provides no experimental data. Hurst believes that the susceptibility to insecticides depends partially on the cuticular permeability, but more fundamentally on the effects on internal tissue receptors which control oxidative metabolism or oxidative enzyme systems. The access of pyrethrins to insects, for example, is facilitated by adsorption and storage in the lipophilic layers of the epicuticle. The epicuticle is to be regarded as a lipoprotein mosaic consisting of alternating patches of lipid and protein receptors which are sites of oxidase activity. Such a condition exists in both the hydrophilic type of cuticle found in larvae of Calliphora and Phormia and in the waxy cuticle of Tenebrio larvae. Hurst explains pyrethrinization as a preliminary narcosis or knockdown phase in which oxidase action is blocked by adsorption of the insecticide on the lipoprotein tissue components, followed by death when further dispersant action of the insecticide results in an irreversible increase in the phenoloxidase activity as a result of the displacement of protective lipids. This increase in phenoloxidase activity is accompanied by the accumulation of toxic quinoid metabolites in the blood and tissues—for example, O-quinones which would block substrate access to normal enzyme systems. The varying degrees of susceptibility shown by different insect species to an insecticide may be explainable not only in terms of differences in cuticle make-up but also as internal factors associated with the stability of oxidase systems. 

The second type of material includes spores, which may or may not produce disease symptoms but which can germinate in the insect gut and give rise to vegetative bacterial cells which in turn may produce, and exoenzymes such as phospholipases (lecithinases) or hyaluronidase. The phospholipases may produce direct toxic symptoms owing to their action on nervous or other phospholipid-containing tissue. Hyaluronidase breaks down hyaluronic acid and produces effects on animal tissue which are morphologically similar to the breakdown of insect gut wall in the presence of microbial insecticide preparations. 

Several compounds are used as insecticides where little is known about their biochemical mode of action or whether they are general toxicants. Some have been around for many years, some are of natural origin and others are living organisms that predate on insects. 

The pyrethrins are valuable insecticidal components of pyrethrum flowers, Chrysanthemum cinerariaefolium (= Tanacetum cinerariifolium) (Compositae/Asteraceae). The flowers are harvested just before they are fully expanded, and usually processed to an extract. Pyrethrum cultivation is conducted in East Africa, especially Kenya, and more recently in Ecuador and Australia. The natural pyrethrins are used as a constituent of insect sprays for household use and as post-harvest insecticides, having a rapid action on the nervous system of insects, whilst being biodegradable and non-toxic to mammals, though they are toxic to fish and amphibians. This biodegradation, initiated by air and light, means few insects develop resistance to the pyrethrins, but it does limit the lifetime of the insecticide under normal conditions to just a few hours. 

Little is known about the nervous systems of cestodes and trematodes except that they probably differ from those of nematodes, since milbemycins and avermectins have no effect on them. However, a highly effective anti schistosomal and antitapeworm agent, praziquantel (see Chapter 54 Clinical Pharmacology of the Anthelmintic Drugs), is known to enhance Ca2+ influx and induce muscular contraction in those parasites, though it exerts no action on nematodes or insects. Some benzodiazepine derivatives have activities similar to those of praziquantel these activities are unrelated to the anxiolytic activities in the mammalian central nervous system. The nerves and muscles in schistosomes and tapeworms are thus interesting subjects for future chemotherapeutic studies. 

Zdarek J., Nachman R. J. and Hayes T. K. (1998) Structure-activity relationships of insect neuropeptides of the pyrokinin/PB AN family and their selective action on pupariation... 

Ryania consists of the powdered stem of the tropical shrub, Ryania speciosa. The extract contains ryanodine and related compounds, and has a low toxicity to mammals. The powder is used as a stomach poison on vegetables and fruit. Ryanodine induces paralysis in insects by direct action on the muscles, resulting in sustained contraction and paralysis. 

The chlorinated insecticides will continue to attract attention because many questions remain outstanding in regard to their mode of action on living organisms and because some of the mechanisms of insect resistance to them are not yet understood. 

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