bioallethrin and decamethrin

Pyrethroid insecticides disrupt nerve function by modifying the gating kinetics of transitions between the conducting and nonconducting states of voltage-gated sodium channels. Pyrethroids modify rat Na(v)1.6+β1+β2 channels expressed in Xenopus oocytes in both the resting state and in one or more states that require channel activation by repeated depolarization. The state dependence of modification depends on the pyrethroid examined: deltamethrin modification requires repeated channel activation, tefluthrin modification is significantly enhanced by repeated channel activation, and S-bioallethrin modification is unaffected by repeated activation. Use-dependent modification by deltamethrin and tefluthrin implies that these compounds bind preferentially to open channels. We constructed the rat Na(v)1.6Q3 cDNA, which contained the IFM/QQQ mutation in the inactivation gate domain that prevents fast inactivation and results in a persistently open channel. We expressed Na(v)1.6Q3+β1+β2 sodium channels in Xenopus oocytes and assessed the modification of open channels by pyrethroids by determining the effect of depolarizing pulse length on the normalized conductance of the pyrethroid-induced sodium tail current. Deltamethrin caused little modification of Na(v)1.6Q3 following short (10ms) depolarizations, but prolonged depolarizations (up to 150ms) caused a progressive increase in channel modification measured as an increase in the conductance of the pyrethroid-induced sodium tail current. Modification by tefluthrin was clearly detectable following short depolarizations and was increased by long depolarizations. By contrast modification by S-bioallethrin following short depolarizations was not altered by prolonged depolarization. These studies provide direct evidence for the preferential binding of deltamethrin and tefluthrin (but not S-bioallethrin) to Na(v)1.6Q3 channels in the open state and imply that the pyrethroid receptor of resting and open channels occupies different conformations that exhibit distinct structure-activity relationships.

Topics: Allethrins; Animals; Binding Sites; Cyclopropanes; Hydrocarbons, Fluorinated; Insecticides; Ion Channel Gating; Kinetics; Membrane Potentials; Mutation; NAV1.6 Voltage-Gated Sodium Channel; Nitriles; Protein Conformation; Pyrethrins; Rats; Receptors, Neurotransmitter; Sodium; Sodium Channels; Structure-Activity Relationship; Xenopus laevis

We expressed rat Na(v)1.6 sodium channels in combination with the rat beta(1) and beta(2) auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 microM), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were ~9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 microM), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 microM), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin approximately 15-fold and that tefluthrin was approximately 10-fold more potent than deltamethrin as a use-dependent modifier of Na(v)1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na(v)1.2 sodium channel coexpressed with the rat beta(1) and beta(2) subunits in oocytes showed that the Na(v)1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na(v)1.2 isoform. These results implicate sodium channels containing the Na(v)1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.

Topics: Allethrins; Animals; Cloning, Molecular; Cyclopropanes; Dose-Response Relationship, Drug; Hydrocarbons, Fluorinated; In Vitro Techniques; Insecticides; Ion Channel Gating; Membrane Potentials; NAV1.6 Voltage-Gated Sodium Channel; Nitriles; Oocytes; Patch-Clamp Techniques; Protein Subunits; Pyrethrins; Rats; Sodium Channels; Structure-Activity Relationship; Transfection; Xenopus laevis

Insecticide in the form of space spray as an ultra low volume (ULV) aerosol are used during epidemics of vector borne diseases. Deltacide, a formulation comprising of three chemicals viz., deltamethrin 0.5 per cent w/v, S-bio-allethrin 0.71 per cent w/v and piperonyl butoxide 8.9 per cent w/v is suitable for ULV application. As this combination is found to be effective in preventing resistance development tackling the population, which had already developed resistance and cause immediate mortality, its synergistic effect was tested in Peet Grady chamber, against three species of mosquitoes, viz., Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus.. Blood fed females were exposed to ULV application of deltacide in a Peet Grady chamber at four dosages viz., 0.005, 0.01, 0.02 and 0.04 ml/m2 and examined for knockdown activity at 10 min interval for 60 min. Thereafter, the mosquitoes were removed from the chamber and maintained in another room having controlled temperature (28+/-2 degrees C) and humidity (60-75%) and observed for recovery, if any, and the per cent knockdown was calculated. Mortality rate after 24 h of holding period was also determined from moribund and dead adults.. Pairwise comparison showed that the effect of deltacide spray varied significantly (P<0.001) among the three species tested. The effectiveness was significantly higher in Ae. aegypti, when compared with that of Cx. quiquefasciatus (P<0.001) and An. stephensi (P<0.05). However, there was no significant difference in the efficacy of deltacide between Cx. quiquefasciatus and An. stephensi. All species of mosquitoes became inactive i.e., knocked down completely within 60 min of exposure at all the dosages tested and mortality observed was 100 per cent after 24 h of exposure.. Deltacide when tested in the form of ULV cold aerosol, the dosage 0.01 ml/m2 was effective against both Ae. aegypti, and An. stephensi, and 0.02 ml/m2 against Cx. quiquefasciatus, causing 100 per cent mortality. The efficacy of ULV application of deltacide against vector mosquitoes needs to be assessed under field conditions.

Topics: Aerosols; Allethrins; Animals; Culicidae; Female; Humans; Insect Vectors; Insecticides; Male; Nitriles; Pesticide Synergists; Piperonyl Butoxide; Pyrethrins

The default assumption that different pyrethroid insecticides, sharing a common mode of action, will show additivity of toxicity has not always been supported by in vitro measures, some of which have indicated antagonism. Our intention was to see whether the antagonism between pyrethroids of different classes seen in vitro could be reproduced in vivo. We therefore investigated the effects of single and combined exposures to two commonly used pyrethroids, deltamethrin (type II) and S-bioallethrin (type I) given intravenously to anaesthetised rats. We used two quantitative measures that are responsive to pyrethroids: the duration of prolongation of hippocampal dentate granule cell inhibition and the amplitude of the abnormal electromyogram discharge. At equi-toxic doses, S-bioallethrin extended the inter-stimulus interval evoking 50% inhibition in the hippocampus by 30+/-2.2 ms, and deltamethrin extended it by 199+/-21 ms. Combined administration of the same doses of deltamethrin and S-bioallethrin extended hippocampal inhibition by 164+/-14 ms, which did not differ significantly from the effect of deltamethrin alone. S-bioallethrin was without any effect on the electromyogram, and produced no significant change in the amplitude of the abnormal muscle discharges evoked by deltamethrin. The increase in arterial blood pressure evoked by the combination was significantly less than that evoked by either pyrethroid alone (p<0.001). In summary, although our electrophysiological indices provide no support for functional antagonism between these two pyrethroids, they also fail to indicate any summation of effect.

Topics: Action Potentials; Allethrins; Animals; Blood Pressure; Drug Synergism; Drug Therapy, Combination; Evoked Potentials; Hippocampus; Injections, Intravenous; Insecticides; Male; Muscle, Skeletal; Neural Inhibition; Nitriles; Pyrethrins; Rats; Rats, Inbred F344; Reflex, Abnormal; Tibial Nerve; Tremor

We evaluated the efficacy of indoor and peridomestic thermal fog applications of deltacide, a synergized mixture of pyrethroids (S-bioallethrin 0.7% w/v, deltamethrin 0.5% w/v and piperonyl butoxide 8.9% w/v) against adult populations of Aedes aegypti in Chennai, Tamil Nadu, India. We bioassayed adult caged mosquitoes, counted indoor resting and human landing adult mosquitoes and assessed the percentage of potential breeding sites with Aedes larvae. The bioassay mortalities indicated that the knockdown and killing effect was greater when fogging was applied inside houses rather than around them. Peridomestic thermal fogging reduced the resting and biting populations by 76% and 40%, respectively for the 3 days after treatment, whereas indoor fogging suppressed adult populations for 5 days.

Topics: Aedes; Allethrins; Animals; Dengue; Hot Temperature; Humans; India; Insect Vectors; Mosquito Control; Nitriles; Pesticide Synergists; Pesticides; Piperonyl Butoxide; Pyrethrins

Previous studies of the conformational behaviour of a group of synthetic pyrethroid insecticides have been extended to a more structurally diverse set. This includes compounds with different backbones and differing stereochemistry, with both Types I and II biological activity. These compounds also encompass a large range of biological activities. A parameterisation of the CHARMM force field for these compounds has been performed and the extra parameters are reported. Conformational sampling, using molecular dynamics (MD), has been performed for each of the 41 active structures. The accessible conformations of each have been characterised by the values of the common torsion angles using hierarchichal cluster analysis (HCA). A further CA, based on the centroids derived from the conformational sampling, identified a conformation common to at least 39 of the 41 structures. The critical torsion angles of this conformation lie at the centre of the molecule about the ester linkage and are defining an extended conformation, which differs from the minimum energy conformation of deltamethrin used previously. This may represent a putative pharmacophore for kill. The methods used here improve significantly on those used previously. The CHARMM force field was parameterised for the compounds and an improved method of conformational sampling, based on centroid clustering, has also been used.

Topics: Allethrins; Cluster Analysis; Computer Simulation; Insecticides; Models, Molecular; Molecular Conformation; Molecular Structure; Nitriles; Pyrethrins; Quantitative Structure-Activity Relationship

Deltacide (S-bioallethrin 0.71% w/v, deltamethrin 0.5% w/v, piperonyl butoxide 8.9% w/v excipients to 100% w/v) and Solfac UL 015 (cyfluthrin 1.5% w/v) were evaluated against the sentinel sugar-fed adults and 4th-instar larvae of Aedes aegypti at 17 storey high-rise apartments in Malaysia using ULV applications. The impact of both insecticides on field populations of Ae. aegypti and Ae. albopictus larvae was monitored weekly using bottle containers. Both Deltacide and Solfac UL 015 showed adulticidal and larvicidal effects. This was the first field trial using Deltacide against dengue vectors in Malaysia and showed its potential for use in dengue vector control programs.

Topics: Aedes; Allethrins; Animals; Dengue; Humans; Insect Vectors; Insecticides; Larva; Malaysia; Nitriles; Pest Control; Piperonyl Butoxide; Pyrethrins

We have recently shown that two pyrethroids, bioallethrin and deltamethrin, affect muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during the period of rapid brain growth. Such early exposure to these pyrethroids can also lead to permanent changes in the MAChR and behavior in the mice as adults. In the present study, male NMRI mice were given bioallethrin (0.7 mg), deltamethrin (0.7 mg), or a 20% fat emulsion vehicle (10 ml) per kilogram of body weight per os once daily between the 10th and 16th postnatal day. The mice were subjected to behavioral tests upon reaching the age of 17 days and at 4 months. Within 1-2 weeks after the behavioral tests the mice were killed by decapitation and crude synaptosomal fractions (P2) were prepared from the cerebral cortex, hippocampus, and striatum. The densities of MAChR were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) specifically bound in the P2 fraction. The proportions of high-affinity (HA) and low-affinity (LA) binding sites of MAChR were assayed in a displacement study using [3H]QNB/carbachol. The behavioral tests at an adult age of 4 months indicated a significant increase in spontaneous motor behavior in both bioallethrin- and deltamethrin-treated mice. There was also a significant decrease and a tendency toward a decrease in the density of MAChR in the cerebral cortex in mice receiving bioallethrin and deltamethrin, respectively. The proportions of HA- and LA-binding sites of MAChR were not changed. This study further supports that disturbances of the cholinergic system during rapid development in the neonatal mouse can lead to permanent changes in cholinergic and behavioral variables in the animals as adults.

Topics: Allethrins; Animals; Animals, Newborn; Brain; Brain Chemistry; DDT; Female; Insecticides; Male; Mice; Motor Activity; Nitriles; Pyrethrins; Quinuclidinyl Benzilate; Receptors, Muscarinic

Ten-day-old NMRI mice were given deltamethrin, bioallethrin, or the vehicle once daily for 7 days. The doses used were as follows: deltamethrin, 0.71 and 1.2 mg/kg body wt; bioallethrin, 0.72 and 72 mg/kg body wt; and 20% fat emulsion vehicle, 10 ml/kg body wt. The mice were killed 24 hr after the last administration, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The densities of the muscarinic and nicotinic receptors were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) and [3H]nicotine, respectively, specifically bound in the P2 fraction. The proportions of high- and low-affinity binding sites of the muscarinic receptors were assayed in a displacement study using [3H]QNB/carbachol. The two types of pyrethroids affected the cholinergic system in the neonatal mouse brain in two different ways. At the lower dose, which did not cause any neurotoxic symptoms, both pyrethroid types affected the muscarinic receptors in the cerebral cortex. Here deltamethrin caused an increase and decrease in the percentage of high- and low-affinity binding sites, respectively, whereas the reverse was observed after bioallethrin treatment. Deltamethrin treatment also caused an increase in the density of nicotinic receptors in the cerebral cortex. The higher doses revealed typical symptoms of pyrethroid poisoning, such as choreoathetosis and tremor for deltamethrin and bioallethrin, respectively. The symptoms declined gradually during each successive day of administration and had disappeared by Day 4. At this dose deltamethrin affected the muscarinic receptors in the hippocampus and the nicotinic receptors in the cerebral cortex, whereas bioallethrin had no apparent effect. This study further supports that the cholinergic system under rapid development in the neonatal mouse is sensitive to xenobiotics.

Topics: Allethrins; Animals; Animals, Newborn; Brain; Cerebral Cortex; Female; Hippocampus; Insecticides; Male; Mice; Nitriles; Pregnancy; Pyrethrins; Receptors, Muscarinic; Receptors, Nicotinic; Tremor

Topics: Allethrins; Animals; Ganglia; Grasshoppers; In Vitro Techniques; Leeches; Membrane Potentials; Models, Neurological; Neurons; Nitriles; Pyrethrins; Species Specificity