Imidacloprid receptor binding studies

To obtain conclusive evidence of the interpretation of the results from receptor binding studies, as summarized above, fonctional studies of nicotinic receptors by electrophysiological techniques would be essential. Such studies have mainly been performed with imidacloprid, as it was available first, using established lab model insects such as cockroaches or other non-target insects, lepidopteran larvae, for example (5, 6, 19). Comparable studies with receptors from true target pests (sucking insects) have yet to be performed they are likely hampered by technical difficulties related to their small size. 

In a recent study, resistance to the neonicotinoid insecticide, imidacloprid, in the brown plant hopper, Nilaparvata lugens, was found to be due to a point mutation at a conserved position in two nAChR subunits. As a result, it reduced the receptor binding of imidacloprid (Liu et al., 2005). 

Neonicotinoids target nicotinic acetylcholine receptors as is mostly known from studies with imidacloprid and conveniently sized lab model insects real target pests have not yet been used for technical reasons. Hence, conclusions, especially those on receptor sensitivity, should be taken with care. On the other hand, radioligand binding studies, which usually do not impose technical hurdles, have been widely performed with neonicotinoids using membranes from target and non-target insects. 

Our studies with aphids clearly suggest that thiamethoxam, like the other examined neonicotoinoids, binds to nicotinic receptors. However, there are clear differences to the other commercial neonicotinoids as documented by a kinetic analysis of competition experiments. While thiamethoxam binds to receptors with nanomolar affinity, micromolar concentrations are required to displace imidacloprid. Further, the interaction between the two compounds is noncompetitive meaning that binding of thiamethoxam reduces the binding capacity of the receptor preparation for imidacloprid but not its affinity. Thiamethoxam shares this unusual mode of inhibition with other neonicotinoids (not commercialized) also featured by an W-Methyl group in die pharmacophore. In the competitive mode, displayed by the other commercial neonicotinoids, the capacity is unchanged, while the affinity is reduced. 

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