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Further research

Pyrethroids are such spectacularly effective compounds; they are ruthlessly effective against insects, yet just mildly toxic to mammals. With this unique profile of biological effects is a complex and sometimes baffling range of properties. One of these has been the topic of the web site - do pyrethroids interact competitively? the answer is far from simple compared with such queries about typical drugs. Still it is always just a case of designing an ingenious enough experiment to whittle the key information out. Some extensions to the current work can be conceived:

1. What effect different dose levels of each pyrethroid would have. For instancenon-toxic doses, or ultra-toxic doses as used in vivo to cause inter-pyrethroid competition.
2. How other pyrethroids, including ones of the same class, or of mixed class, compare in this paradigm.
3. How animals with gene-knockout for subtypes of sodium channels function in these tests. This kind of research would be better once knowledge on sodium channel expression is extended.
4. Does it matter which pyrethroid is applied first, and for how long? This may be important when considering slower acting intracellular mechanisms.

Mechanisms behind paired-pulse inhibition

One piece of knowledge which would help in understanding, at least as far as the paired-pulse inhibition model is concerned, is how exactly neurons in the dentate gyrus network. A detailed appreciation of the typical connectivity, including the biochemical communication pathways involved, would complement this field as well as many others concerned with structure and function of central brain areas.

Sub-sites of interaction

Another question of interest is where exactly do pyrethroids bind to their various targets? A solid answer could help in interpreting the results on multi-pyrethroid interactions. Finding specific binding sites, especially on the sodium channel, which can be specifically targeted with antagonists would provide a means to develop novel drugs for pyrethroid poisoning. However the huge range of pyrethroids and their targets makes comprehensive study of this a massive task. Work on resistance conferring mutations of channel proteins in Drosophila has proved insightful, however there is no consensus as to how pyrethroids exert their actions on membrane channels and other intracellular targets [Pittendrigh et al, 1997; Soderlund et al, 2000].

Keeping pragmatic

The sheer challenge of understanding pyrethroids is perhaps the best thing about studying them; it inevitably leads to creative thinking and innovation in order to unravel the tightly bound scroll of knowledge. It's important not to be too quixotic when planning further research. It is tempting to become entranced by the bizarre pharmacology of pyrethroids, and fascinating trying to elucidate the deeper mechanisms, yet one must keep one's sights on the greater goals. Currently pyrethroids are just pesticides, made to protect crops from the little jaws of bugs (although see below for other potential uses).

Frontier uses for pyrethroids... antidepressant?

If non-toxic insect repellents are developed, what will we do with pyrethroids? The compounds have been intensely researched and are surely one of the most potent and specific modulators of neural function known to science. Surely they can find other uses than poisoning bugs?

Some recent research reveals that deltamethrin is a particularly potent inducer of brain-derived neurotrophic factor (BDNF) synthesis [Imamura et al, 2005]. The increased expression of BDNF mRNA and protein were seen for at least 48 hours after deltamethrin was withdrawn, and was dependent on calcium ion influx and associated phosphorylation events. This effects was specific to Type II pyrethroids, not occurring with Type I.

BDNF has some close associations with neuroplasticity, and a lack of it has been associated with depression [Slattery et al, 2003]. In rats BDNF was increased in the cerebral cortex and hippocampus, which are key sites for plasticity in relation to depression. Deltamethrin or other perhaps undiscovered analogues could become effective antidepressants by boosting scant levels of BDNF in the brain. Whether there is a good therapeutic window will need to be investigated; however it is possible that side effects will be inseparable from increased BDNF expression, sharing a common cause of hyperexcitability

Alternative to insecticides for protecting crops

Our current means of pest control basically consists of ways to incapacitate or kill insects, using neurotoxins. This tactic is maladaptive, as insects are a vital part of the ecosystem, as well as having negative affects upon other creatures. Yet spreading toxins over crops remains a steadfast way of protecting them from damage, which is the prerogative of the farmer. Insecticides are cheap and provide a real short term benefit to some communities. Until alternatives are presented these poisoning tactics will persist.

Recently work into the nature of chemosensory systems has been taking off, and with it some new ideas about pest control. Insects have tiny nervous systems which are largely reflexive, and much of their sensory interpretation of the environment is through odour. It may be possible to find stable scents that selectively repel insects, and even specific species, from crops while posing no risk to them or other creatures. Developing compounds that exploit the innate, hardwired olfactory system of insects would be essential, as there is some room for adaptive learning in insects [Faber et al, 1999] . Drosophila has been partially characterised in this respect. It will become increasingly possible to screen for compounds which attract or repel insects, providing new ways of controlling their behaviour, and to increase crop yield [Firestein, 2001].