Insecticides

lecture 7

insecticides

• compounds which kill insects

• necessary for crop protection, human health and veterinary use

• target signalling proteins in neurotransmission and muscle contraction → all target NS except for diamides (muscles)

• designed to be pest selective

• finite lifespan due to resistance

• often based on natural neurotoxins

targets of insecticides

• DDT and pyrethroids → VGSCs

• organophosphates and carbamates → AChE inhibition

• neonicitinoids (nicotine), sulfoximines and butenoides → nAChRs persisnent agonists

• organichlorines and phenylpyraxoles → ligand gated Cl channels

• diamides → agonise ryanodine receptor to cause paralysis

early insecticides

• effective

• not pest selective

• high toxicity to humans and non-pest animals

• eg. DDT, cyclodienes, organochlorines, organophosphates and carbamates

safer insecticides

• good selectivity for target proteins in pests

• relatively non-toxic to humans and non-pest animals

• pyrethroids first → based on naturally occuring pyrethrins from pyrethrum daisy

pyrethroids

• target voltage gated sodium channels

• sensitise channel to voltage to reduce inactivation and slow deactivation

• massive gain of function → persistent depolarisation

• insect selectivity can be traced to a single AA difference

neonicitinoids

• target nAChRs

• agonists very selective to insect nAChRs

• developed from natural toxins → nicotine and epibatidine

• cannot be metabolised by AChE → large gain in function via persistent activation

• systemic and so can be applied via seed treatment → no indiscriminate spraying

  • distributes through plant in growth

  • target insects which feed on the plant only → but in pollen so can expose pollinators

• some banned in EU in 2013

pyrethroids in humans

• causes redness, tingling and burning pain in extremities

• symptoms similar to that of primary erythromelalgia (PE) → caused by gain of function of Na_v1.7

• Na_v1.7 is sensitised to voltage so less depolarisation os needed for activation

• PE mutations involved in Na channel sensitivtity (DIIS4-S5 linker and DIIS5)

  • where pyrethroid resistance mutations can occur

• activates channel very quickly and by a lot while tail currents increase excitability

• humans are sensitive to pyrethroids a relatively low concentrations

• badly effected farmers may have Na_v1.7 PE mutations

nicotinoids and annelid nAChRs

• neonicitinoids target pest insects with high insect selectivity, using systemic treatment

• studied annelid nAChR receptors → earthworms and leeches are not pests

• tested 2 nicitinoids (one banned and one not)

• causes substantial contraction of annelid muscle at low concentrations

  • agonises nAChR

  • limiting to seed treatment is beneficial

  • test on other beneficial invertebrates