Afoxolaner
[CAS# 1093861-60-9]

Identification

• Classification: Biochemical >> Inhibitor >> Neuronal signaling >> GABA receptor agonist
• Name: Afoxolaner
• Synonyms: 4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide
• Molecular Formula: C₂₆H₁₇ClF₉N₃O₃
• Molecular Weight: 625.87
• CAS Registry Number: 1093861-60-9
• EC Number: 832-051-7
• SMILES: C1C(=NOC1(C2=CC(=CC(=C2)Cl)C(F)(F)F)C(F)(F)F)C3=CC=C(C4=CC=CC=C43)C(=O)NCC(=O)NCC(F)(F)F

Properties

• Solubility: Insoluble (3.4E^-5 g/L) (25 °C), Calc.^*
• Density: 1.53±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

Safety Data

• Hazard Symbols: GHS08;GHS09 Warning
• Risk Statements: H361-H361d-H410
• Safety Statements: P203-P273-P280-P318-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Afoxolaner is a novel chemical compound classified as an insecticide and acaricide, primarily used in veterinary medicine to control ectoparasites such as fleas and ticks in dogs and cats. This compound is a member of the isoxazoline class, which has gained prominence for its efficacy and safety profile in the treatment of parasitic infestations.

The discovery of afoxolaner can be traced back to the early 2000s when researchers at Merial, a global animal health company, were exploring new methods for controlling flea and tick infestations. The search for effective treatments led to the identification of isoxazoline derivatives, which demonstrated a novel mode of action against arthropods by targeting specific neurotransmitter systems. Afoxolaner was first synthesized and characterized during this research phase, showcasing potent activity against a broad spectrum of ectoparasites.

Afoxolaner functions by inhibiting the gamma-aminobutyric acid (GABA) receptor and the glutamate-gated chloride channels in the nervous system of parasites. This mechanism disrupts normal neurological function, leading to paralysis and eventual death of the target organisms. Its selectivity for insect and arachnid targets allows for a favorable safety profile in mammals, making it a preferred choice for treating parasitic infections in pets.

In practical applications, afoxolaner is incorporated into various formulations, including chewable tablets and topical treatments. The compound has been marketed under different brand names, with its effectiveness in controlling fleas and ticks contributing to its popularity among veterinarians and pet owners. The rapid onset of action and prolonged residual effects—often lasting for up to a month—make afoxolaner an attractive option for routine parasite prevention.

The introduction of afoxolaner has significantly impacted veterinary practice, providing an effective solution for managing flea and tick infestations. Its broad-spectrum activity, ease of administration, and safety in animals have established it as a vital component in pet healthcare.

Despite its efficacy, ongoing research continues to explore the potential for afoxolaner in treating other parasitic diseases and expanding its use in different animal species. As the understanding of isoxazolines grows, there may be opportunities to develop new derivatives with enhanced properties or specific applications.

In summary, afoxolaner is a key compound in the veterinary pharmacological landscape, providing a reliable means to control ectoparasites and improve the health and well-being of pets.

References

2014. Afoxolaner against fleas: immediate efficacy and resultant mortality after short exposure on dogs. Parasite (Paris, France), 21.
DOI: 10.1051/parasite/2014045

2014. The intravenous and oral pharmacokinetics of afoxolaner used as a monthly chewable antiparasitic for dogs. Veterinary Parasitology, 201(3-4).
DOI: 10.1016/j.vetpar.2014.02.021

2024. Efficacy of Afoxolaner (NexGard®) in the treatment of furuncular myiasis caused by Dermatobia hominis fly (Diptera: Cuterebridae) in naturally infested dogs. Veterinary Parasitology: Regional Studies and Reports, 54.
DOI: 10.1016/j.vprsr.2024.101076