title: Neonicotinoid insecticide toxicology: mechanisms of selective action.
abstract: The neonicotinoids, the newest major class of insecticides, have outstanding potency and systemic action for crop protection against piercing-sucking pests, and they are highly effective for flea control on cats and dogs. Their common names are acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam. They generally have low toxicity to mammals (acute and chronic), birds, and fish. Biotransformations involve some activation reactions but largely detoxification mechanisms. In contrast to nicotine, epibatidine, and other ammonium or iminium nicotinoids, which are mostly protonated at physiological pH, the neonicotinoids are not protonated and have an electronegative nitro or cyano pharmacophore. Agonist recognition by the nicotinic receptor involves cation-pi interaction for nicotinoids in mammals and possibly a cationic subsite for interaction with the nitro or cyano substituent of neonicotinoids in insects. The low affinity of neonicotinoids for vertebrate relative to insect nicotinic receptors is a major factor in their favorable toxicological profile.
authors.affiliation: Environmental Chemistry and Toxicology Laboratory, Department of Environmental Science, Policy and Management, University of California, Berkeley, California 94720-3112, USA. tomizawa@nature.berkeley.edu
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tomizawa
authors.forename: John E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D010078:Oxazines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011978:Receptors, Nicotinic / Q000378:metabolism*; D000077922:Thiamethoxam; D013844:Thiazoles
chemical_list: D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D010078:Oxazines; D011725:Pyridines; D011978:Receptors, Nicotinic; D013844:Thiazoles; C464485:acetamiprid; D000077922:Thiamethoxam