For dogs and cats, nitenpyram is given orally (1 mg/kg) to control fleas for a brief period of time. After 30 minutes of treatment, fleas begin to drop off of the animals, and one dose can keep animals safe for one to two days[1]. Because nitenpyram is so lipophilic, it is taken orally after meals to stimulate bile flow, which aids in dissolving the substance and improves gastrointestinal absorption of the medication. When given orally to dogs and cats, it is quickly and entirely absorbed from the GI tract in less than 90 minutes and entirely eliminated in the urine in 48 hours. In the liver, nitinpyram is hydroxylated and then conjugated. Nitenpyram does not build up in bodily tissues; instead, its conjugates are eliminated in the urine. In dogs and cats, the plasma half-life of nitenpyram is 3 and 8 hours, respectively. Nitenpyram's plasma half-life is probably prolonged in animals with liver and/or kidney issues[1].

Absorption, Distribution and Excretion
Nitenpyram is rapidly and practically completely absorbed after oral administration. Peak levels occur approximately 80 minutes after dosing in dogs; approximately 40 minutes in cats. Elimination half-lives are: approximately 3 hours for dogs; 8 hours for cats. Nitenpyram is excreted primarily as conjugated metabolites in the urine and excretion is complete within 48 hours of dosing. In dogs, approximately 3% of a dose is excreted in feces; in cats approximately 5% is excreted in the feces.
Nitenpyram is administered PO in pill form to kill fleas in both dogs and cats. It is absorbed rapidly, with maximal blood concentrations reached within 1.2 hr and 0.6 hr in dogs and cats, respectively. ... The compound is rapidly eliminated, with >90% excreted in the urine within 24-48 hr, primarily as unchanged nitenpyram.

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Metabolism / Metabolites
BACKGROUND: Nitenpyram is a member of the economically important neonicotinoid class of insecticides. The in vivo metabolism of nitenpyram is not well characterized, but cytochrome P450 activity is the major mechanism of resistance to neonicotinoids identified in insect pests, and P450s metabolize other neonicotinoids including imidacloprid. RESULTS: Here, we used the GAL4-UAS targeted expression system to direct RNA interference (RNAi) against the cytochrome P450 redox partners to interrupt P450 functions in specific tissues in Drosophila melanogaster. RNAi of the mitochondrial redox partner defective in the avoidance of repellents (dare) in the digestive tissues reduced nitenpyram mortality, suggesting an activation step in the metabolism of nitenpyram carried out by a mitochondrial P450. RNAi of the mitochondrial cytochrome P450 Cyp12a5, which is expressed in the digestive tissues, resulted in the same phenotype, and transgenic overexpression of Cyp12a5 increased nitenpyram sensitivity. CONCLUSION: These results suggest that in vivo metabolism of nitenpyram by the mitochondrial P450 CYP12A5 results in the formation of a product with higher toxicity than the parent compound.

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Biological Half-Life
Elimination half-lives /after oral dosing/ are: approximately 3 hours for dogs; 8 hours for cats.

Toxicity Summary
IDENTIFICATION AND USE: Nitenpyram is neonicotinoid insecticide that controls aphids, leafhoppers, thrips, whiteflies on rice and glasshouse crops. It is also used to control fleas in dogs and cats. HUMAN STUDIES: There are no data available. ANIMAL STUDIES: The following adverse events are listed in decreasing order of reporting frequency. Cats: hyperactivity, panting, lethargy, itching, vocalization, vomiting, fever, decreased appetite, nervousness, diarrhea, difficulty breathing, salivation, incoordination, seizures, pupil dilation, increased heart rate, and trembling. Dogs: lethargy/depression, vomiting, itching, decreased appetite, diarrhea, hyperactivity, incoordination, trembling, seizures, panting, allergic reactions including hives, vocalization, salivation, fever, and nervousness. The frequency of serious signs, including neurologic signs and death, was greater in animals under 2 pounds of body weight, less than 8 weeks of age, and/or reported to be in poor body condition. In some instances, birth defects and fetal/neonatal loss were reported after treatment of pregnant and/or lactating animals. ECOTOXICITY STUDIES: The toxic effect of nitenpyram on the brain of juvenile Chinese rare minnows (Gobiocypris rarus) was investigated by determining the oxidative stress, and acetylcholinesterase (AChE) activity. The superoxide dismutase (SOD) activities did not significantly change after long-term exposure to nitenpyram. A noticeable increase of catalase (CAT) activities was observed on the brain tissues under nitenpyram treatments. The malondialdehyde (MDA) content increased markedly under 0.1 mg/L nitenpyram treatments. The AChE activities decreasing under 2.0 mg/L nitenpyram. Changes in the antioxidant enzyme activities in zebrafish are reported for nitenpyram. Nitenpyram was highly toxic to earthworm (Eisenia fetida), and can significantly inhibit fecundity and cellulase activity of E. fetida, and it was also damaging to the epidermal and midgut cells of earthworms.

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Non-Human Toxicity Values
LD50 Rat (male) oral 1680 mg/kg
LD50 Rat (female) oral 1575 mg/kg
LD50 Rat (male) dermal >2000 mg/kg
LD50 Rat (female) dermal >2000 mg/kg
For more Non-Human Toxicity Values (Complete) data for Nitenpyram (6 total), please visit the HSDB record page.

[1]. Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals. J Vet Pharmacol Ther. 2010 Aug;33(4):315-22.

[2]. Efficacy and longevity of nitenpyram against adult cat fleas (Siphonaptera: Pulicidae). J Med Entomol. 2003 Sep;40(5):678-81.

Nitenpyram is a C-nitro compound consisting of 2-nitroethene-1,1-diamine where one of the nitrogens bears ethyl and (6-chloro-3-pyridinyl)methyl while the other nitrogen carries a methyl group. It has a role as a neonicotinoid insectide. It is a C-nitro compound and a monochloropyridine. It is functionally related to a 2-chloropyridine.
Nitenpyram is an insecticide used in agriculture and veterinary medicine to kill external parasites of pets. It is a neonicotinoid, a neurotoxin that blocks neural messages and binds particularly tightly in the central nervous system of insects, causing rapid death.
Nitenpyram has been reported in Streptomyces canus with data available.
See also: Lufenuron; Nitenpyram (component of); Lufenuron; Milbemycin Oxime; Nitenpyram (component of).

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Mechanism of Action
Nitenpyram is in the class of neonicotinoid insecticides. It enters the systemic circulation of the adult flea after consuming blood from a treated animal. It binds to nicotinic acetylcholine receptors in the postsynaptic membranes and blocks acetylcholine-mediated neuronal transmission causing paralysis and death of the flea. Nitenpyram is 3500x more selective for insect alpha-4beta-2 nicotinic receptors than in vertebrate receptors. It does not inhibit acetylcholinesterase.

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Therapeutic Uses
VET: Nitenpyram inhibits the nicotinic acetylcholine receptor. It is used to treat Ctenocephalides spp in dogs and cats ... . It is toxic to fleas for only 24-48 hr and is normally used in combination with an insect growth regulator to provide continuous flea control.
VET: Nitenpyram is indicated as a flea adulticide in dogs and cats that are, at a minimum, 2 pounds in weight and 4 weeks old. It does not repel fleas or ticks and does not reliably kill ticks, flea eggs, larvae or immature fleas. Nitenpyram may be effective for treating fly larvae (maggots) of various species. Fleas begin to fall from treated animals about 30 minutes after dosing and a single dose can protect animals for 1-2 days.

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Drug Warnings
VET: The following adverse events are based on post-approval adverse drug experience reporting. Not all adverse reactions are reported to FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data. The following adverse events are listed in decreasing order of reporting frequency. Cats: hyperactivity, panting, lethargy, itching, vocalization, vomiting, fever, decreased appetite, nervousness, diarrhea, difficulty breathing, salivation, incoordination, seizures, pupil dilation, increased heart rate, and trembling. Dogs: lethargy/depression, vomiting, itching, decreased appetite, diarrhea, hyperactivity, incoordination, trembling, seizures, panting, allergic reactions including hives, vocalization, salivation, fever, and nervousness. The frequency of serious signs, including neurologic signs and death, was greater in animals under 2 pounds of body weight, less than 8 weeks of age, and/or reported to be in poor body condition. In some instances, birth defects and fetal/neonatal loss were reported after treatment of pregnant and/or lactating animals.

C11H15CLN4O2

270.72

270.088

150824-47-8

3034287

Light yellow to yellow solid powder

1.3±0.1 g/cm3

417.2±45.0 °C at 760 mmHg

72ºC

206.1±28.7 °C

0.0±1.0 mmHg at 25°C

1.568

1.9

1

5

5

18

306

0

CCN(CC1=CN=C(C=C1)Cl)/C(=C/[N+](=O)[O-])/NC

CFRPSFYHXJZSBI-DHZHZOJOSA-N

InChI=1S/C11H15ClN4O2/c1-3-15(11(13-2)8-16(17)18)7-9-4-5-10(12)14-6-9/h4-6,8,13H,3,7H2,1-2H3/b11-8+

(E)-1-N'-[(6-chloropyridin-3-yl)methyl]-1-N'-ethyl-1-N-methyl-2-nitroethene-1,1-diamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (7.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)