Neurotoxins insecticides

A striking feature of the toxic compounds considered so far is that many of them are neurotoxic to vertebrates or invertebrates or both. The nervous system of animals appears to be a particularly vulnerable target in chemical warfare. Not altogether surprisingly, all the major types of insecticides that have been commercially successful are also neurotoxins. Indeed, in 2003, neurotoxic insecticides accounted for over 70% of total insecticide sales globally (Nauen 2006). 

As Muller had prophesied and indeed hoped, DDT stimulated the discovery of more synthetic insecticides. DDT relatives included chlordane, toxaphene, aldrin, dieldrin, endrin, and heptachlor. Popular substitutes for DDT s family included organophosphates such as parathion, which is a powerful neurotoxin, and carbamates, which are also highly toxic to people. Unlike DDT, parathion and aldicarb have killed and injured many farm workers. Malathion was later developed to be several hundred times less toxic than parathion. 

Natural pyrethrins are a neurotoxin and repel, knock down, and kill by contact with insects at a low concentration. On the other hand, they have ideal features for household insecticides because of their quite low dermal and oral toxicides to warm-blooded animals. Neither plants other than pyrethrum nor synthetic insecticides have been reported to have such properties. Numerous synthetic pyrethroids have been developed by chemists since the complicated chemical structure of natural pyrethrins was elucidated in the middle of the twentieth century. Allethrin was the first synthetic pyrethroid put into practical use. 

Sabaliunas et al. (2000) showed that a Daphnia pulex immobilization test (Daphtoxkit F) was far more sensitive than Microtox to a mixture of insecticides seqnestered in SPMDs. This is not surprising because the OCPs and pyrethroid pesticides present in the enriched SPMD extracts are neurotoxins, and the effect thresholds can be much lower than narcosis-type toxicants. Thus, if insecticides are the contaminants of concern, the Daphtoxkit F approach may have some advantage over Microtox. 

Leptophos [21609-90-5], O-methyl 0-(4-bromo-2,5-dichlorophenyl) phenylphosphonothioate (80) (mp 71°C), is soluble in water to 0.03 mg/L. The rat oral LD5Qs are 53, 45 mg/kg. Leptophos has been extensively used as a cotton insecticide but is a delayed neurotoxin. 

Psilocybin can be isolated and crystallized or synthesized to nearly 100% purity. Research indicates that Psilocybe mushrooms produce a bitter alkaloid as an insecticide to protect itself from predators. In humans, psilocybin is a neurotoxin that can cause hallucinations. 

Psilocybin is a neurotoxin that targets the central nervous system and serotonin receptors in the brain when it is ingested. It is believed that the mushroom produces this bitter toxin as an insecticide to protect itself from predators. 

Lu, D., Pava-Ripoll, M., Li, Z., and Wang, C. (2008). Insecticidal evaluation of Beauveria bassiana engineered to express a scorpion neurotoxin and a cuticle degrading protease. Applied Microbiology and Biotechnology, 81, 515-522. 

The powerful action of some natural products on the central nervous system may suggest their potential value in insect control. If their mammalian toxicity can be reduced by structural modification they may be useful insecticides. Cartap, a rice insecticide, is a bisthiocarbamate. Its structure was based on that of the natural product, nereistoxln, a neurotoxin isolated from shellfish, and it is likely that an in vivo metabolic conversion of cartap to nereistoxln or related compound is responsible for its activity (11). 

Acylpolyamines are potent neurotoxins that have been shown to inhibit calcium-ion channels and selectively block glutamate, NMDA (A-methyl-o-aspartate), or AMPA (a-amino-3-hydroxy-5-methylisoxazol-4-propionate) receptors, which is probably the basis of their insecticidal properties. As a result, acylpolyamines have received considerable attention as tools for studying neurotransmitter function and may be of therapeutic... 

Another biosensor was developed for AN-a(s) by Devic et al. (2002) that addressed the lack of sensitivity and specificity of detection of some bioassays. An acetylcholinesterase was engineered to increase its sensitivity and a combination of mutants was used to obtain increased analyte specificity. The sensitivity of detection achieved was reported to be below 1 nM/L. By using a four-mutant set of acetylcholinesterase variants, two of which are sensitive to AN-a(s) and two are sensitive to the insecticides, an improvement in the specificity of the biosensor for the cyanobacterial neurotoxin was achieved (Devic et al., 2002). 

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