Studies on the action of chlordimeform in cockroaches

The effects of chlordimeform [N-(2-methyl-4-chlorophenyl)-N′,N′-dimethylformamidine] on amine regulatory mechanisms in insects were studied. Chlordimeform inhibits monoamine oxidase (MAO) from cockroach heads in vitro, and the MAO substrates serotonin and norepinephrine accumulate in poisoned insects in vivo. Chlordimeform synergizes the toxicity of tryptamine, another MAO substrate. The significance of these findings in relation to the mode of action of chlordimeform is discussed.     

Effects of chlordimeform on vascular smooth muscle

The effects of chlordimeform on agonist-induced contractions of rabbit aortic strips and on calcium flux in the deadventitiated strips have been studied. Chlordimeform antagonizes contractions induced by several vasoactive agents, with the order of antagonism being potassium . histamine > serotonin > norepinephrine, and decreases the rate of contraction of strips exposed to each of the four agonists. Muscles contracted by each of the agonists are rapidly relaxed by application of chlordimeform, although in the case of norepinephrine the relaxation only proceeds to approximately one-half of the maximal tension. The rate of washout of ⁴⁵Ca from the media-intimal layer of the rabbit aorta was increased by chlordimeform, but the norepinephrine-induced decrease in the rate of washout of ⁴⁵Ca was not affected by chlordimeform. Chlordimeform did not affect ⁴⁵Ca uptake by the media-intimal strips. The results of this study indicate that chlordimeform probably interferes with loosely bound calcium to a greater extent than it does with more tightly bound stores.     

Effects of organosilicon pyrethroid‐like insecticides on nerve preparations of American cockroaches and crayfish

Quaternary organosilicon pyrethroid‐like ethers (five compounds) and alkanes (three compounds) were used for neurophysiological tests. Their activities in inducing repetitive firing in the central nervous cord of the American cockroach (Periplaneta americana) were evaluated by an extra‐cellular recording method. The ethers were more active than the corresponding alkanes. The ability of the compounds to cause conduction blockage was also measured using the same nerve preparations, but the effects were too weak to allow definitive activity values to be determined. The compounds prolonged the sodium tail‐current in the crayfish giant axon under voltage clamp conditions. The rate of decay of the tail‐current changed in parallel with the reported insecticidal activity against P americana. These findings indicated that tail‐current activity was the most useful nerve parameter in predicting insecticidal activity. Regression analysis of the numerical data together with those reported for other alkanes revealed that the higher the tail‐current activity, the higher the insecticidal activity when a structural feature and the hydrophobicity were considered separately. The insecticidal activity of the ethers was about seven‐fold higher than that of the alkanes with equivalent tail‐current activity and hydrophobicity. Variations in insecticidal activity were parabolically correlated with the hydrophobicity [(log P)_opt = 9.1] when other factors were similar. © 2001 Society of Chemical Industry     

Effects of chlordimeform on rectus abdominis muscle of frog

The effects of chlordimeform on rectus abdominis muscle of frog were investigated. Chlordimeform (10^?3M) caused a slow contraction, and at lower concentration (10^?5–10^?3M) it inhibited the acetylcholine-induced contraction in noncompetitive manner. When chlordimeform was applied to the muscle of Rana catesbiana, K⁺-induced contraction was also inhibited in noncompetitive manner. Whereas it had no effect on caffeine-induced contraction.Chlordimeform-induced contraction was not affected by respective addition of d-tubocurarine (10^?4M), procaine (10^?3M), or eserine (0.3 mM), which results were same as that of K⁺-induced contraction. Chlordimeform, at lower concentration (10^?5–10^?3M), inhibits the acetylcholine- and K⁺-induced contractions probably owing to depression of not only the sensitivity of endplate but also the excitability of cell membrane.     

Effects of chlordimeform on mitochondria from eggs of Spodoptera littoralis

Mitochondria were isolated from eggs of Spodoptera littoralis. With succinate (+pyruvate) as substrate, respiratory control ratios between 1.70 and 2.54 were obtained. Uncouplers and the energy transfer inhibitor oligomycin influenced these mitochondria in the well-known manner. The uncoupling activity of chlordimeform in vitro was very weak and decreased with increasing age of the eggs. Electron transport in mitochondria from chlordimeform-treated eggs was not uncoupled. Therefore, it is concluded that the ovicidal effect of this pesticide is not due to its uncoupling effect.     

Honey-bee abdomen assays of hemolymph from stressed and externally poisoned American cockroaches

Blood from cockroaches stressed by having their mouthparts sealed or by being dehydrated by contact with silica aerogel, administered into the opened wounds of freshly excised honey bee abdomens, produced neuromuscular reaction that was monitored and recorded as characteristic myograms. When blood became too viscous or unobtainable during the terminal stages of stress, coxal muscle was substituted. Abdomens used for assay were also used for toxicological studies, comparing their survival time with untreated abdomens. Intact and decapitated cockroaches were equally desiccated by contact with silica aerogel to determine if presence or absence of the coordinating center had any bearing on stress. Fragments of coxal muscle from the intact cockroaches deactivated 10 bee abdomens in 15 hr while coxal muscle from the decapitated cockroaches deactivated only one out of 10 abdomens. Blood from cockroaches poisoned by oral administrations of boric acid solution was readily available, clear, and free-flowing, and produced myograms showing periods of lethargy followed by deep convulsions. Portions of these myograms resembled symptoms of lethargy and convulsions produced by boric acid solution when it was administered directly into the bee abdomens.     

The in vivo sensitivity of ATPases to DDT,DDE, and physical immobilization in American cockroaches

American cockroaches injected with sublethal doses of DDT (0.75 μg/roach) at 5-day intervals showed a 40% reduction in oligomycin-sensitive Mg²⁺ATPase from muscle homogenates, and a 23% reduction of Na⁺-K⁺ATPase from nerve cords. Thus, the maximum effect measured occurred with the same enzyme and tissue as determined from in vitro studies. The metabolite, DDE, used at 15 μg per roach, gave no significant change in activity of the ATPase system following injection. In contrast, high single doses of DDT (7.5 μg/roach) and 100 μg DDE and dicofol per roach caused over 30% increase in oligomycin-sensitive Mg²⁺ATPase of muscle and a 10–15% increase in Na⁺-K⁺ATPase of nerve cords measured 24 and 48 hr later. While a similar response was observed for Mg²⁺ATPase activities in cockroaches that were immobilized, the increase in enzyme activities were much greater than that caused by the pesticides.     

Effects of chlordimeform and lindane on monoamine levels in the central nervous system of the american cockroach, Periplaneta americana L

The effects of chlordimeform and lindane on levels of 5-hydroxytryptamine, tryptophan, and N-acetyl dopamine were studied in the cerebral ganglia of the american cockroach, Periplaneta americana. The effects of chlordimeform on nerve cord levels of 5-hydroxytryptamine, tryptophan, dopamine, and octopamine, and the effect of lindane on cerebral ganglia levels of dopamine were also investigated in this species. Topical applications of chlordimeform deplete 5-hydroxytryptamine and tryptophan from the cerebral ganglia whereas levels of n-acetyl dopamine are elevated. The effect of chlordimeform on these compounds is dose-dependent. Similar chlordimeform-induced effects are observed in the nerve cord, and octopamine levels are also depleted in this tissue following treatment with chlordimeform. A biphasic response to chlordimeform is observed in the nerve cord for dopamine levels with a 40% decrease evident after 2 hr and a 30% increase apparent after 6 hr. In contrast to chlordimeform, lindane does not affect 5-hydroxytryptamine and tryptophan levels in the cebral ganglion but low doses of this insecticide effect increases in brain levels of dopamine and n-acetyl dopamine.     

Similar pharmacological actions of chlordimeform and local anesthetics

The toxic symptoms of the pesticide, chlordimeform, resemble those observed following systemic local anesthetic overdose. In view of similarities in the chemical structures of chlordimeform and the local anesthetic agent phenacaine, additional comparisons between the actions of chlordimeform and local anesthetics were made. Chlordimeform had effects on the frog sciatic nerve preparation similar to those of local anesthetics (i.e., blocked conduction, increased threshold, prolonged refractory period). Chlordimeform was 0.6 times as active as procaine, less active in the ionized form, and more active on the desheathed preparation. Chlordimeform lethality was reduced by pretreatment with diazepam or pentobarbital, but not by diphenylhydantoin, trimethadione, or mephenesin pretreatment. These pretreatments have a comparable effect on local anesthetic toxicity. Chlordimeform lethality was slighly increased by agents possessing “local anesthetic activity” such as imipramine, pyribenzamine, and phenoxybenzamine. These and other results indicate that a number of the pharmacological and toxic actions of chlordimeform in mammals may be due to actions that are similar to those of local anesthetic agents.     

Insect glutathione S-transferase: Separation of transferases from fat bodies of American cockroaches active on organophosphorus triesters

Several glutathione S-transferases which catalyze the conjugation of reduced glutathione with organophosphorus triesters were separated from fat bodies of adult female American cockroaches, Periplaneta americana (L.). Two transferases (I, V) were active on diazinon and three transferases (II, III, IV) were active on methyl parathion. The transferase (I) active on the pyrimidinyl moiety of diazinon was distinguishable from the other transferases on the O-methyl portion of methyl parathion, as shown by chromatographic properties, and additionally it was almost inactive or less active on 3,4-dichloronitrobenzene, methyl iodide, p-nitrobenzyl chloride, trans-cinnamaldehyde, and 1,2-epoxy-3-(p-nitrophenoxy)propane. Transferase II had high activities with “aryl” and “aralkyl” compounds, transferase III with “epoxide” and “alkene,” and transferase IV with “alkyl,” “aryl,” and “aralkyl” compounds. This indicated that the transferases had overlapping substrate specificities. The molecular weight was 35,000–37,000 for both of the enzymes active on methyl parathion and diazinon. The pH optima with methyl parathion and diazinon were about 8.5 and 6.5, respectively. At a glutathione concentration of 5 mM, Michaelis constants were 0.28 and 0.13 mM for methyl parathion and diazinon, respectively.     

Tissue analysis and hemolymph translocation of [14C]chlorpyrifos sorbed from treated surfaces by American cockroaches

Using radiotracer methodology and dissection techniques it was demonstrated that [¹⁴]chlorpyrifos and/or its ¹⁴C-labeled metabolite(s) concentrated mainly in the gut tissues and malpighian tubules of American cockroaches, Periplaneta americana (Linnaeus), following sorption from a treated surface. Significantly lower (P ≤ 0.10) amounts of ¹⁴C were present in testes samples and no radioactive material was detected in brain tissue. After 41.5–48 hr of exposure of adult male American cockroaches to sublethal concentrations of [¹⁴C]chlorpyrifos, radioactivity was detected in the hemolymph of all cockroaches tested. The hemolymph accounted for 30.83% of the total sorbed ¹⁴C. A parabiotic experiment confirmed translocation of chlorpyrifos and/or its ¹⁴C-labeled metabolite(s) in hemolymph.     

Quantitative structure-activity studies of substituted benzyl chrysanthemates: 1. Correlations between symptomatic and neurophysiological activities against American cockroaches

A number of substituted benzyl (1R)-trans-chrysanthemates and related compounds were synthesized. Their symptomatic activities in terms of levels which induce convulsions as well as cause death in American cockroaches were determined by injection with and without application of synergists as inhibitors of metabolism. The neuroexcitatory and neuroblocking activities were also determined in terms of minimum effective concentrations to induce repetitive train of impulses and conduction blockage, respectively, to central nerve cords excised from the cockroaches and immersed in Ringer's solution. Correlations between symptomatic and neurophysiological activities were analyzed quantitatively with the aid of molecular hydrophobicity parameter and regression analysis. Each symptomatic activity from which the effect of metabolism is eliminated was found to be analyzable by means of a linear combination of indices for two types of neurophysiological activity when the transport factor is separated by using the hydrophobicity parameter. A closer correlation was found between neuroblocking activity and the “convulsive” effect than between neuroexcitatory activity and the “convulsive” effect, whereas both neurophysiological effects operate together on the cockroaches resulting in paralysis and death.     

Quantitative structure-activity studies of substituted benzyl chrysanthemates: 2. Physicochemical substituent effects and neurophysiological and symptomatic activities against American cockroaches

The substituent effects on the symptomatic and neurophysiological activities of a number of substituted benzyl (1R)-trans-chrysanthemates against American cockroaches were quantitatively analyzed using electronic, hydrophobic, and steric parameters. The effects were shown to be highly specific to substituent positions except for those on the neuroblocking activity. Steric effect of substituents represented by van der Waals volume was found to play the most significant role in determining the variation in each activity. Peculiar substituent effects depending upon the bulkiness and position of substituents, which had been observed in the toxicity of this class of compounds, can be rationalized by the present analysis indicating that the optimum van der Waals volume of substituents is largest at the ortho and smallest at the para position.     

Monoamine oxidase inhibition and brain catecholamine levels in the rat following treatment with chlordimeform

Norepinephrine and dopamine levels in rat brain increase by 51.7 and 70.3%, respectively, within 14 hr of intraperitoneal injection of 24 mg chlordimeform/kg wet wt. An inhibition of monoamine oxidase (MAO) activity in mitochondrial extracts from brains and livers of chlordimeform-treated rats occurred concomitantly with the elevation of catecholamine levels. In the brain extract the oxidative deamination of tyramine was inhibited by 8.1% and that of 2-phenylethylamine by 54.5%, whereas in the liver preparation the extent of inhibition using these substrates was 23.8 and 31.1%, respectively. The results suggest specific inhibition of type B MAO, and the conclusion was substantiated by use of clorgyline, a specific inhibitor of type A MAO. The results are discussed in light of the observation that rats which are exposed to sublethal concentrations of chlordimeform display pronounced behavioral changes.     

Recent studies on the effects of DDT and pyrethroid insecticides on nervous activity in cockroaches

A summary is given of the results of three sets of electrophysiological experiments on the American cockroach (Periplaneta americana). The effects of DDT and S-bioallethrin [bioallethrin (S)-cyclopentenyl isomer] on single giant axons were studied using the voltage-clamp technique. Whereas both molecules induced long tails of inward (sodium ion) current, the voltage and time-dependency of these tails differed. With DDT, the tail was proportional to the activation of the peak current and decreased with the duration of the pulse, suggesting that the molecules were bound to open sodium channels and delayed their closing. With S-bioallethrin, the voltage dependency of the tail was different from that of the peak current, and the tail current increased exponentially with the duration of the depolarisation, suggesting that the pyrethroid insecticide modified resting (or silent) sodium channels into slowly activating channels. Modified action potentials, mimicking those produced by the two molecules, were computed on the basis of these results. Deltamethrin, one of the most potent pyrethroid insecticides, was applied topically on a leg mechanoreceptor and was found to have little effect on the local ‘receptor potential’ but to inhibit action potential production. The effects of topical applications of deltamethrin on the dorsal part of the abdomen, on nervous activity in the abdominal connectives, were studied under different experimental conditions. The results suggest that the insecticide molecules diffused rapidly through the cuticle, were concentrated in the haemolymph, and eventually reached the central nervous system, where they inhibited nerve activity.     

Repellancy and contact toxicity of clove bud oil and its constituents against German cockroaches,Blatella germanica (Dictyoptera: Blattellidae), under laboratory conditions

Abstract

The German cockroach, Blattella germanica L. (Dictyoptera: Blattellidae), an invasive pest of human habitats, is distributed throughout the world, except in Antarctica. They have developed resistance against chemical pesticides used for the management of their populations. Numerous essential oils and their constituents have been tested; however, the insecticidal activities of clove bud powder, oil, and their constituents have not yet been tested against the German cockroaches. Thus, in this study, clove bud powder, oil, and their major constituents, eugenol and eugenol acetate, were evaluated for their contact toxicity and repellancy against adult German cockroaches under laboratory conditions. The clove bud powder applied at 30?mg/cm² killed 92% of German cockroaches at 6?hours after treatment (HAT). Similarly, clove bud oil, eugenol and eugenol acetate applied at 4.00?ml/cm² provided 95%, 85%, and 87% German cockroach mortality at 24, 6, and 24 HAT, respectively. At 2.0?ml/cm², clove bud oil repelled 80% of German cockroaches within 30?min. In contrast, eugenol and eugenol acetate repelled 85% at 1.0?ml/cm² and 2.5?ml/cm², respectively, at 0.5 HAT. Based on this study, clove bud powder, oil, eugenol, and eugenol acetate could be environmentally friendly tools for the management of German cockroaches.     

Effects of a formulation of neem extract on six species of cockroaches (Orthoptera: Blaberidae,Blattidae and Blattellidae)

Margosine-0®, a commercial preparation of neem seed extract, was tested for its effects as a toxicant, growth inhibitor, or repellent against six species of cockroaches —Blatta orientalis L.,Blattella germanica (L.),Byrsotria fumigata Guérin-Méneville,Gromphadorhina portentosa (Schaum),Periplaneta americana (L.), andSupella longipalpa (F.) (Orthoptera: Blaberidae, Blattidae, and Blattel-lidae). Last-instar nymphs of these species fed Lab-Chow® pellets impregnated with neem extract at a rate of 0.5 ml/pellet showed increased mortality and retarded development. All lst-instar nymphs ofB, orientalis, B. germanica andS. longipalpa died after consuming treated Lab-Chow pellets. Topical application of 2 μl of Margosine-0 to the abdomens of last-instarB. orientalis nymphs, as well as injection of 0.5 μl, resulted in reduction of growth and increased mortality. Placing lst-instarB. orientalis nymphs on a surface treated with the neem extract had no notable effect. In a choice test,P. americana adults immediately preferred the pellets treated with 0.5 ml of neem extract, but pint cardboard cartons treated with 1.5 ml extract repelled them.     

The effect of single and combined doses of chlordimeform and permethrin on cAMP and cGMP levels in the moth,Mamestra configurata Wlk

Treatment of adult males of the moth, Mamestra configurata, with chlordimeform caused large increases (up to 27-fold) in the concentration of cAMP in the head, thorax, and abdomen but had little effect on cGMP. This pesticidal effect, termed A⁺G⁰, likely results from the interaction of chlordimeform (or a metabolite) with an octopamine-sensitive adenylate cyclase present in the brain and other tissues. Treatment of moths with permethrin caused substantial increases (up to 3.4-fold) in the concentration of cGMP in the head and thorax but had little effect on cAMP. This effect, termed A⁰G⁺, may result from a disturbance of cholinergic function. Treatment of moths with a combined dose of chlordimeform and permethrin caused increases in the concentration of both cAMP and cGMP (A⁺G⁺ effect) in the head and thorax and had a synergistic effect on mortality. The synergistic effect on mortality appears to be caused by the disruption of distinct and different physiological systems by the A⁺G⁰ and A⁰G⁺ pesticides. The hypothesis that A⁺G⁰ and A⁰G⁺ pesticides, when combined, will exhibit synergism is supported by examples from the literature.