Afoxolaner

Afoxolaner is an insecticide and acaricide that belongs to the isoxazoline chemical compound group. It is used to kill fleas and ticks in small animals.

Afoxolaner

Clinical data
Pronunciation	/eɪˌfɒksoʊˈlænər/ ay-FOK-soh-LAN-ər
Trade names	Nexgard, Frontpro
Other names	4-[(5RS)-5-(5-Chloro-α,α,α-trifluoro-m-tolyl)-4,5-dihydro-5-(trifluoromethyl)-1,2-oxazol-3-yl]-N-[2-oxo-2-(2,2,2-trifluoroethylamino)ethyl]naphthalene-1-carboxamide
AHFS/Drugs.com	International Drug Names
License data	US DailyMed: Afoxolaner
Routes of administration	By mouth
ATCvet code	QP53BE01 (WHO)
Legal status
Legal status	CA: ℞-only US: ℞-only[1][2] EU: Rx-only[3] OTC (RU)[4]
Pharmacokinetic data
Bioavailability	74% (Tmax = 2–4 hours)[4]
Elimination half-life	14 hours[4]
Excretion	Bile duct (major route)
Identifiers
IUPAC name 4-{5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl}-N-{2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl}naphthalene-1-carboxamide
CAS Number	1093861-60-9
PubChem CID	25154249
DrugBank	DB11369
ChemSpider	28651525
UNII	02L07H6D0U
KEGG	D10361
ChEMBL	ChEMBL2219412
CompTox Dashboard (EPA)	DTXSID50148921
ECHA InfoCard	100.267.822
Chemical and physical data
Formula	C26H17ClF9N3O3
Molar mass	625.88 g·mol−1
3D model (JSmol)	Interactive image
Chirality	Racemic mixture
SMILES O=C(CNC(=O)c1ccc(C2=NOC(c3cc(Cl)cc(C(F)(F)F)c3)(C(F)(F)F)C2)c2ccccc12)NCC(F)(F)F
InChI InChI=1S/C26H17ClF9N3O3/c27-15-8-13(7-14(9-15)25(31,32)33)23(26(34,35)36)10-20(39-42-23)18-5-6-19(17-4-2-1-3-16(17)18)22(41)37-11-21(40)38-12-24(28,29)30/h1-9H,10-12H2,(H,37,41)(H,38,40) Key:OXDDDHGGRFRLEE-UHFFFAOYSA-N

Mechanism

Alfoxolander is a GABA receptor antagonist, which stops chloride transmission in nerves and muscles resulting in paralysis 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 over mammalian 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 and vertebrates.^[7]

Use

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]

Legal status

The marketing authorization was granted by the European Medicines Agency in February 2014, for Nexgard,^[3][8] and in January 2015, for Nexgard Spectra.^[9][10]

Brand names

Afoxolaner is the active ingredient of the veterinary medicinal products Nexgard,^[3] Frontpro, and Nexgard Spectra (in combination with milbemycin oxime).^{[9][11][12][13]} They are indicated for the treatment and prevention of flea infestations, and the treatment and control of tick infestations in dogs and puppies (8 weeks of age and older, weighing 4 pounds (~1.8 kilograms) of body weight or greater) for one month.^[14]