Axonic poisons

Several classes of insecticides are axonic poisons, which interfere with axonal conduction. Therefore, a brief account of axonal conduction will first be given. 

By comparison, DDT and plifenate modified sodium channels rapidly but the lifetime of the channels in the modified open state was much shorter (10-20 msec) (type I effect). Thus, axons poisoned with these compounds showed long trains of potentials with very little effect on the resting potential at low concentrations. These two groups of compounds apparently represent two extreme cases of a continuous variation in the rates at which sodium channels reach the modified open state and return to the resting state. Most of the other compounds tested were intermediate and showed repetitive activity as well as some decrease in the resting potential (Table I). Since the kinetics... 

Pyrethroids. More accurately described as the synthetic pyrethroids, this group of compounds has been used extensively in wood preservation for control of both beetles and termites. Activity, cost and performance characteristics vary depending upon the specific compound but most readily accepted for use in wood preservative formulations are permethrin, cypermethrin, deltamethrin, bifenthrin and cyfluthrin. In terms of activity against wood boring beetles, cyfluthrin is estimated to be 20 times more effective than permethrin, 10 times as effective as cypermethrin and twice as effective as deltamethrin when compared in laboratory evaluative procedures. However, in practice other factors need to be considered, particularly the relative vapour pressures (and therefore evaporative loss) and, in wood in soil contact, the rate of biotransformation by colonising bacteria. The pyrethroids are effective as neurotoxins, and are axonic poisons. 

Pyroles and phenylpyrozoles. The pyroles such as chlorfenapyr act as metabolic toxins and work by uncoupling oxidative phosphorylation in the mitochondria. In contrast the phenylpyrozole, fipronil has a mode of action similar to the cyclodiens (e.g. aldrin) and acts as an axonic poison. 

The contractile proteins of the spindle apparatus must draw apart the replicated chromosomes before the cell can divide. This process is prevented by the so-called spindle poisons (see also colchicine, p. 316) that arrest mitosis at metaphase by disrupting the assembly of microtubules into spindle threads. The vinca alkaloids, vincristine and vinblastine (from the periwinkle plant. Vinca rosea) exert such a cell-cycle-specific effect. Damage to the nervous system is a predicted adverse effect arising from injury to microtubule-operated axonal transport mechanisms. 

Interspecific differences are also known for some naturally occurring poisons. Nicotine, for instance, is used as an insecticide and kills many insect pests at low doses, yet tobacco leaves constitute a normal diet for several species. As indicated earlier, most strains of rabbit eat Belladonna leaves without ill effects, whereas other mammals are easily poisoned. Natural tolerance to cyanide poisoning in millipedes and the high resistance to the powerful axonal blocking tetrodotoxin in puffer fish are examples of the tolerance of animals to the toxins they produce. 

The neurotoxin, tetrodotoxin, a highly potent poison from the puffer fish, blocks the conduction of nerve impulses along axons and so leads to respiratory paralysis by binding very tightly to the Na+ channel and blocking its action. 

Neurons in primary cultures are extremely sensitive to poisoning by clostridial toxins (Habermann et ai, 1988 Williamson et ai, 1996). Moreover, primary neuronal cultures mimic many basic features of neural tissue in vivo, providing much easier access of toxins to neuronal membranes and synaptic structures. By applying clostridial toxins to primary cultured neurons it is also possible to study the possible role of the target proteins in axon elongation, synaptogenesis or neuronal survival. 

Again, the critical experiments which demonstrated the mechanisms of this process were performed by Hodgkin, by Keynes, and by A. F. Huxley. They used in their experiments the biggest nerve they could find - the giant axon of the squid, which is so wide, being up to a millimetre in diameter, that it is relatively easy to inject test substances down inside it and to study their effects. They first showed that nervous conduction is dependent on energy metabolism. Nerves poisoned with cyanide, which prevents oxida-... 

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