Neonicotinoids interaction with other

Different Modes of Binding Interaction with Other Neonicotinoids... 

The synthesis of this compound was first described by Agro Kanesho [16]. Further preparations have been discussed in Section 29.2.3.4. As with all neonicoti-noids, AKD-1022 (12) interacts with nicotinic acetylcholine receptors however, it is much less potent than imidacloprid (8) and other commercial neonicotinoids. In particular, this has been demonstrated with Myzus and Drosophila membranes [23], as well as on American cockroaches [33]. It has been speculated that AKD-1022 (12), as a basic molecule, is ionized in the fluids of insects and, therefore, reaches the synapse only slowly through the lipophilic cuticles and the ion barriers. During retarded movement, the compound is prone to decompose, e.g., due to partial hydrolysis mediated enzymatically and/or non-enzymatically [33]. Therefore, acyclic nitroguanidines such as 19 may also contribute to the insecticidal activity observed in glasshouse and field studies. 

These data showed that thiamethoxam (13), like imidadoprid (8) and the other neonicotinoids, binds with high affinity to nicotinic receptors [57]. However, there are clear differences to the other commercial neonicotinoids, as documented by a kinetic analysis of competition experiments [56]. While [ H]thiamethoxam (13) binds to receptors with nanomolar affinity, micromolar concentrations are required to displace [ H]imidadoprid (8). Further, the interaction between the two compounds is non-competitive , meaning that binding of thiamethoxam (13) reduces the binding capacity of the receptor preparation for imidadoprid (8) but not its affinity. Thiamethoxam (13) shares this unusual mode of inhibition with other neonicotinoids (not commercialized) containing a N-methyl group as pharmacophore substituent [56, 58]. 

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