Afoxolaner: mechanism of action, applications and safety

General Description

Afoxolaner is an isoxazoline-class insecticide and acaricide that targets ligand-gated chloride ion channels, specifically inhibiting the gamma-aminobutyric acid (GABA) gated channels. This disrupts the normal flow of chloride ions, leading to increased neuronal activity, paralysis, and death of insects. Afoxolaner is effective against fleas, ticks, mites, and other ectoparasites. It is commonly used in oral or chewable tablet form for the treatment and prevention of flea and tick infestations in dogs. A single dose provides long-lasting protection and helps control diseases associated with these parasites. While generally safe, precautions should be taken in pregnant dogs, puppies, and small-sized dogs. It's important to follow veterinary advice, handle and store the product properly, and monitor for adverse reactions.

Figure 1. Afoxolaner

Mechanism of action

Afoxolaner is an insecticide and acaricide belonging to the isoxazoline class, and it exerts its action by targeting ligand-gated chloride ion channels. Specifically, it inhibits the gamma-aminobutyric acid (GABA) gated channels, which are responsible for the transmission of chloride ions from the presynaptic membrane to the postsynaptic membrane. This blockade disrupts the normal flow of chloride ions, leading to increased neuronal activity and ultimately causing excessive excitation and death of insects. By inhibiting GABA-gated channels, afoxolaner disrupts the neurotransmission process critical for the proper functioning of the insect's nervous system. The excessive neuronal activity triggered by this mechanism overwhelms the insect's neural circuitry, resulting in paralysis, seizure-like activity, and eventual death. This targeted mode of action makes afoxolaner highly effective against a wide range of pests, including fleas, ticks, mites, and other ectoparasites. Overall, afoxolaner's mechanism of action highlights its efficacy as an insecticide and acaricide by selectively disrupting the GABA-gated chloride channels, leading to neuroexcitation and subsequent mortality in insects and mites. ¹

Applications

Afoxolaner is a widely used medication for the treatment of flea and tick infestations in dogs. It belongs to a class of drugs called isoxazolines, which are highly effective in controlling these parasites. Afoxolaner works by inhibiting the nervous system of fleas and ticks, leading to their paralysis and subsequent death.This medication is available in the form of oral tablets or chewable tablets, making administration easy and convenient for pet owners. A single dose of afoxolaner provides long-lasting protection against fleas and ticks for up to several weeks. It starts killing existing fleas within hours of administration and continues to protect against reinfestation. Afoxolaner is particularly useful in the prevention and treatment of diseases caused by fleas and ticks, such as flea allergy dermatitis and tick-borne infections. By eliminating these parasites, it helps improve the overall health and well-being of dogs. In conclusion, afoxolaner is a reliable and effective solution for tackling flea and tick problems in dogs, providing long-lasting protection and promoting their overall health. ²

Safety

Afoxolaner is generally considered safe when used according to prescribed dosage and administration guidelines. However, there have been reports of adverse reactions in Collie dogs when given a higher dosage (5 times the recommended dose) of afoxolaner, such as diarrhea and vomiting. However, there are certain considerations to keep in mind. Pregnant dogs, puppies under 8 weeks old, and dogs weighing less than 2kg should be used with caution and under veterinary advice. While afoxolaner effectively exposes fleas and ticks to its active ingredient, there is still a potential risk of disease transmission through parasitic vectors. If the dog refuses to consume the medication directly, it can be mixed with their food. Unused chewable tablets should be returned to the original packaging, and it's important to wash hands after handling the product. Expired products should never be used. To ensure safety, store the medication in a place inaccessible to children. It is always recommended to follow the guidance of a veterinarian and closely monitor the dog for any adverse reactions. ³

Reference

1. Otranto D. NEXGARD®. Afoxolaner, a new oral insecticide-acaricide to control fleas and ticks in dogs. Editorial. Vet Parasitol. 2014;201(3-4):177-178.

2. Shoop WL, Hartline EJ, Gould BR, et al. Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs. Vet Parasitol. 2014;201(3-4):179-189.

3. Drag M, Tielemans E, Mitchell E. Safety of oral afoxolaner formulated with or without milbemycin oxime in homozygous MDR1-deficient collie dogs. J Vet Pharmacol Ther. 2022;45(4):373-379.