To recap:

Nicotine in the form of tobacco extracts was reported in 1690 as the first plant-derived insecticide, followed by the pyrethrins from pyrethrum flowers and rotenone from derris roots in the early 1800s. Synthetic organics in the 1940s to the 1970s largely replaced inorganics and botanicals with the introduction of organophosphates, methylcarbamates, organochlorines, and pyrethroids. With each new chemical class, resistant strains were soon selected to limit their effectiveness.  Many of the remaining gaps in pest control capabilities were filled recently by the neonicotinoids, which combine outstanding effectiveness with relatively low toxicity to vertebrates.   

The neonicotinoids are the only major new class of insecticides developed in the past three decades. Worldwide annual sales of neonicotinoids are approximately one billion dollars, accounting for 11%–15% of the total insecticide market. They are readily absorbed by plants and act quickly, at low doses, on piercing-sucking insect pests (aphids, leafhoppers, and whiteflies) of major crops. The neonicotinoids are poorly effective as contact insecticides and for control of lepidopterous larvae.

Although crop protection is the major use for neonicotinoids, pest insect control on pets or companion animals is also a significant market. The neonicotinoids have unique physical and toxicological properties as compared with earlier classes of organic insecticides.  

The neonicotinoids and pyrethroids have higher selectivity factors for insects versus mammals than the organophosphates, methylcarbamates, and organochlorines. This is attributable to both target site specificity and detoxification. Of the commercial neonicotinoids, acetamiprid, IMI, and thiacloprid are the most toxic to birds, and thiacloprid to fish. Several neonicotinoids are harmful to honeybees, either by direct contact or ingestion, but potential problems can be minimized or avoided by treating seeds and not spraying flowering crops

The neonicotinoids are nicotinic agonists that interact with the nAChR in a very different way than nicotine, which confers selectivity to insects versus mammals. These differences provide the neonicotinoids with favorable toxicological profiles.

Source:

NEONICOTINOID INSECTICIDE TOXICOLOGY:
Mechanisms of Selective Action
Motohiro Tomizawa and John E. Casida
Environmental Chemistry and Toxicology Laboratory, Department of Environmental
Science, Policy and Management, University of California, Berkeley
Annu. Rev. Pharmacol. Toxicol. 2005. 45:247–68

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