Selective toxicity of neonicotinoids attributable to specificity of insect and mammalian nicotinic receptors.
Neonicotinoids, the most important new class of synthetic insecticides of the past three decades, are used to control sucking insects both on plants and on companion animals. Imidacloprid (the principal example), nitenpyram, acetamiprid, thiacloprid, thiamethoxam, and others act as agonists at the insect nicotinic acetylcholine receptor (nAChR). The botanical insecticide nicotine acts at the same target without the neonicotinoid level of effectiveness or safety. Fundamental differences between the nAChRs of insects and mammals confer remarkable selectivity for the neonicotinoids. Whereas ionized nicotine binds at an anionic subsite in the mammalian nAChR, the negatively tipped ("magic" nitro or cyano) neonicotinoids interact with a proposed unique subsite consisting of cationic amino acid residue(s) in the insect nAChR. Knowledge reviewed here of the functional architecture and molecular aspects of the insect and mammalian nAChRs and their neonicotinoid-binding site lays the foundation for continued development and use of this new class of safe and effective insecticides.
Tomizawa
Motohiro
M
Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA. tomizawa@nature.berkeley.edu
Casida
John E
JE
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001665:Binding Sites; D002490:Central Nervous System / Q000378:metabolism; D004351:Drug Resistance; D066298:In Vitro Techniques; D007313:Insecta / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008322:Mammals; D009538:Nicotine / Q000494:pharmacology / Q000633:toxicity; D010944:Plants; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity
D000470:Alkaloids; D007306:Insecticides; D011978:Receptors, Nicotinic; D009538:Nicotine