Alfoxolander is aGABA receptor antagonist, which stops chloride transmission in nerves and muscles resulting inparalysis with the paralysis resulting in death for the insect. Alfoxolaner is more selective for GABA repectors in insects than mammals making it safe to give to an animal in amounts that are still lethal to insects.[5]
Selectivity for insect overmammalian GABA-receptors has been demonstrated for other isoxazolines.[6] The selectivity might be explained by the number of pharmacological differences that exist between GABA-gated chloride channels of insects andvertebrates.[7]
Afoxolaner is given orally and is then rapidly distributed into the systemic circulation, when a tick or flea feeds on the blood of the host it ingests the afoxolaner and becomes paralysed. Thus fleas and ticks must first feed on the host for the drug to be effective. Afoxolaner has been given up to five times the therapeutic dose without causing intoxication.[5]
The marketing authorization was granted by theEuropean Medicines Agency in February 2014, for Nexgard,[3][8] and in January 2015, for Nexgard Spectra.[9][10]
Afoxolaner is theactive ingredient of the veterinary medicinal products Nexgard,[3] Frontpro, and Nexgard Spectra (in combination withmilbemycin oxime).[9][11][12][13] They are indicated for the treatment and prevention offlea infestations, and the treatment and control oftick infestations indogs andpuppies (8 weeks of age and older, weighing 4 pounds (~1.8 kilograms) of body weight or greater) for one month.[14]
^abPapich, Mark (2016).Saunders Handbook of Veterinary Drugs (4th ed.). Elsevier.ISBN978-0-323-24485-5.
^Casida JE (April 2015). "Golden age of RyR and GABA-R diamide and isoxazoline insecticides: common genesis, serendipity, surprises, selectivity, and safety".Chemical Research in Toxicology.28 (4):560–566.doi:10.1021/tx500520w.PMID25688713.
^Hosie AM, Aronstein K, Sattelle DB, ffrench-Constant RH (December 1997). "Molecular biology of insect neuronal GABA receptors".Trends in Neurosciences.20 (12):578–583.doi:10.1016/S0166-2236(97)01127-2.PMID9416671.S2CID5028039.
