Nitenpyram is a neonicotinoid, a neurotoxin that blocks neural messages and used in agriculture and veterinary medicine to kill external parasites of pets. Imidacloprid 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. Nitenpyram was introduced into the United States in 1994 as a veterinary flea control treatment, structural pest and crop insecticide, and seed treatment. It has been used orally in dogs, cats, and some wildlife species for over 10 years. After ingestion, it begins killing adult fleas within 30 minutes, and effects continue for up to 48 hours. Though nitenpyram is used to kill adult fleas quickly on an infected animal, it does not kill insect eggs and has no long-term activity. Thus, it is not effective as a long-term flea preventative; however, it can be repeatedly applied over the course of several days to eradicate a single instance of infestation. Nitenpyram can be combined with a longer-term flea preventative like fipronil or lufenuron to prevent reinfestation. Neonicotinoids for veterinary use are considered to have a low order of toxicity for domestic animals and there are no reports of nitenpyram intoxication.