Neonicotinoid insecticides nicotinic acetylcholine receptors

Neonicotinoids are potent broad-spectrum insecticides that exhibit contact, stomach and systemic activity. Acetamiprid, imidacloprid, nitenpyram, thiamethoxam and thiacloprid are representatives of the neonicotinoid insecticides (Figure 1). The mechanism of action is similar to that of nicotine, acting on the central nervous system causing irreversible blocking of postsynaptic nicotinic acetylcholine receptors (nAChR). Neonicotinoid insecticides are often categorized as antagonists of the... 

Some toxic consequences of neonicotinoids for nontarget beneficial aquatic and terrestrial arthropods such as bees can be expected since these creatures have nicotinic acetylcholine receptors as functional components of the cholinergic system similar to those of insect pests. Surprisingly, neonicotinoid toxicity to numerous nontarget insect species and wildlife marker vertebrates, for example, rainbow trout, is lower than expected. In general, the environmental safety of neonicotinoids surpasses that of other insecticides. 

Neonicotinoid, Insecticide, Resistance, Nicotinic Acetylcholine Receptor, Nilaparvata lugens... 

A nicotinic acetylcholine receptor point mutation (Y151S) conferring insecticide resistance causes reduced agonist potency to a range of neonicotinoids (N. S. Millar, Univ. College London, UK)... 

The cholinergic system in insects is the main target of insecticides. One class of molecules, the neonicotinoids, induces direct activation of the neuronal nicotinic acetylcholine receptors (nAChRs). In the honey bee these receptors are mainly distributed in the olfactory pathways that link sensory neurons to antennal lobes and mushroom bodies. These structures seem to play an important role in olfactory conditioning. We have previously shown that cholinergic antagonists injected in different parts of the brain impaired the formation and retrieval of olfactory memory. We then advanced the hypothesis that, through the activation of the nAChR, the neonicotinoid imidacloprid (IMI) would lead to facilitation of the memory trace. 

S. Soloway, in Neonicotinoid Insecticides and the Nicotinic Acetylcholine Receptor (Eds. 1. Yamamoto, J. E. Casida), Springer Press, Berlin, Heidelberg, New York, 1999, pp. 71-89. 

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. 

In 1984, Mark E. Schroeder and Roger F. Flattum at Shell explored for nithiazine as the example, at which site these nitromethylene insecticides interact to effect their pharmacological activity. In cockroaches, the nicotinic acetylcholine receptor turned out to be the target. [140] In insects, the expression of these receptors is limited to the nervous system. There they reach a density, which is comparable only to the electric organ of the South American electric eel (Electro-phorus electricus). [ 141 ] From ligand displacement studies with nerve cell receptors of the American cockroach (Periplaneta americana), the honey-bee (Apis mellifera) and the common housefly (Musca domestica), the a-subrmit of the receptor became evident as the prime locus of interaction for neonicotinoids. 

The cholinergic synapse is the key target area for aU major insecticides. Nicotine and the neonicotinoids bind to the postsynaptic nicotinic acetylcholine receptor. 

Neonicotinoid insecticides act agonistically on insect nicotinic acetylcholine receptors (nAChRs). Like imidacloprid (IMI), all neonicotinoids bind with high affinity (Iso-values 1 nM) to binding sites on... 

Maienfisch P, Brandi F, Kobel W, RindUsbacher A, Senn R (1999). CGA 293 343 a novel, broad-spectrum neonicotinoid insecticide. In Yamamoto I, Casida JE (eds) Nicotinoid insecticides and the nicotinic acetylcholine receptor. Springer, Tokyo, pp 177-209 Majumdar DN (1952) Alkaloidal constituents of Withania somnifera. Curr Sci 21 46 Majumdar DN (1955) Withania somnifera. II. Alkaloidal constituents and their chemical characterization. Ind J Pharm 17 158-61... 

Another biological target for many insecticides is the nervous system of the insect because this can result in selective toxicity. The neonicotinoids, in group 4, work by this mechanism and act on insect nicotinic acetylcholine receptors (nACtiR). Nicotine, the namesake of the nACtiR has been used for pest control since the century [33], However nicotine is hazardous to people and has limited effectiveness as an insecticide. Nicotine and its analog epibatidine, isolated from a tropical poisonous frog, exist mainly in the pro-tonated form at physiological pH. They are examples of the nicotinoid family and are toxic to mammals. 

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