Neonicotinoids metabolism

Many pesticides are not as novel as they may seem. Some, such as the pyre-throid and neonicotinoid insecticides, are modeled on natural insecticides. Synthetic pyrethroids are related to the natural pyrethrins (see Chapter 12), whereas the neo-nicotinoids share structural features with nicotine. In both cases, the synthetic compounds have the same mode of action as the natural products they resemble. Also, the synthetic pyrethroids are subject to similar mechanisms of metabolic detoxication as natural pyrethrins (Chapter 12). More widely, many detoxication mechanisms are relatively nonspecific, operating against a wide range of compounds that... 

In general, neonicotinoids (except for nitenpyram) are metabolized slowly in plants, and remain mainly as the parent compounds. The definition of crop residues is for the acetamiprid and imidacloprid parent molecule. The definition of crop... 

Imidacloprid will be used to illustrate the fate of neonicotinoid insecticides (Figure 8.32). Imidacloprid is reduced (1) and then becomes the triazine derivative (2). It can be hydroxv-lated at the imidazole ring to become themonohydroxylated derivatives (3 and 4). Reduction of parent imidacloprid to the nitroso derivative (5) occurs in some animal species. Imidacloprid is also cleaved to become the nitroiminoimidazololidine (6). Further metabolism involves olefin formation (7), glycine conjugation (8), and others. 

The metabolism of neonicotinoids in vertebrates, insects, and plants has many common features. It may result in cleavage and the separation of the heterocyclic and pharmacophore moieties, or modifications of a pharmacophore in an intact parent molecule. Oxidations, reductions, and elimination reactions are the major mechanisms that result mostly in a reduced or diminished insecticidal potency of the metabolites. Dehydration of the 4-hydroxyimidazolidinyl resulting in a formation of the imidazolinyl (olefin) or reduction of the N-nitroimine ( = N—NO2) to N-nitrosoimine ( = N—NO) group (Figure 5) are examples of a... 

Thiamethoxam. This new insecticide is classed as a member of the important neonicotinoid family, which act as agonists of the nicotinic acetylchoMne receptor. Thiamethoxam has systemic activity, meaning that a level of it or active metabolic products is maintained in the plant and ingested by the attacking insects. It is especially used in the protection of tomato crops. 

AKD 1022 (18) as well as thiamethoxam (17) (Chapter 29.2.3) can form the open-chain neonicotinoid 3 by ring cleavage, either by hydrolysis (see synthesis methods in this chapter) or metabolism (Scheme 29.2.1.4). 

In this connection the usefiilness of local reactivity descriptors for understanding drug metabolism of neonicotinoids, the electrophilic Fukui function of THIAM 6 was investigated (20). 

Neonicotinoids do not act as a homogenous class of insecticides. Radioligand receptor binding assays revealed two classes of neonicotinoids described here as competitive and non-competitive , respectively, relative to [ H]imidacloprid. Differences in affinity, mode of displacement, number of binding sites and temperature sensitivity suggest that thiamethoxam binds in a way unique among the commercial neonicotinoids. Metabolic transformation is not relevant for its insecticidal effects. 

Like other insecticides, thiamethoxam is transformed in the insect, crop, soil and other compartments to variable degrees to yield products that may not or may be active in their own right. An example for the latter case m the neonicotinoid class is imidacloprid, which is metabolized via hydroxylated intermediates to an olefin product that is more active than the parent compound by one order of magnitude in aphids screens and in receptor binding 20. 21). 

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