Selective toxicity neonicotinoids

Tomizawa M and Casida JE (2003) Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors. Annual Reviews in Entomology 48 339-364. 

Yamamoto, L, Yabuta, G., Tomizawa, M., Saito, T., Miyamoto, T., and Kagabu, S. 1995. Molecular mechanism for selective toxicity of nicotinoids and neonicotinoids. 

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. 

In contrast, the neonicotinoids are not protonated and therefore bind differently, resulting in greater activity on insects than manunals. It is this selective toxicity that has led to extensive use of the neonicotinoids and they represent about 20% of the global insecticide market [34]. Worldwide sales of neonicotinoid insecticides are estimated at 1 billion [35]. Imidacloprid and thiacloprid are examples of neonicotinoid insecticides. 

Nicotine and neonicotinoids are agonists, both of which act at the nicotinic acetylcholine receptor -Na" /K+ ionophore. The structural differences between the insect and mammalian receptors define the selectivity of neonicotinoid toxicity to insects and nicotine toxicity to vertebrates. The proposed concept of the neonicotinoid electronegative pharmacophore... 

In contrast to S-(—)-nicotine (1 rat oral LD50 = 50-60 mg a.i. kg , high mammalian oral and dermal toxicity), neonicotinoid insecticides display excellent selectivity profiles that are largely attributable to spedfity for insect versus vertebrate nAChRs. This is exemplified by the fact that the radioligand [ H]-7 serves... 

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