Afoxolaner

Last updated
Afoxolaner
Afoxolaner structure.svg
Clinical data
Pronunciation /eɪˌfɒksoʊˈlænər/ ay-FOK-soh-LAN-ər
Trade names Nexgard, Frontpro
Other names4-[(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
Routes of
administration 		By mouth
ATCvet code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 74% (Tmax = 2–4 hours) [4]
Elimination half-life 14 hours [4]
Excretion Bile duct (major route)
Identifiers
  • 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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.267.822 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C26H17ClF9N3O3
Molar mass 625.88 g·mol−1
3D model (JSmol)
Chirality Racemic mixture
  • 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=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

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.

Contents

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]

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]

References

  1. ↑ "Nexgard- afoxolaner tablet, chewable". DailyMed. 7 March 2024. Retrieved 16 June 2024.
  2. ↑ "Nexgard- afoxolaner tablet, chewable". DailyMed. 13 March 2024. Retrieved 16 June 2024.
  3. 1 2 3 "Nexgard EPAR". European Medicines Agency. 27 March 2013. Retrieved 16 June 2024.
  4. 1 2 3 "Frontline Nexgard (afoxolaner) for the Treatment and Prophylaxis of Ectoparasitic Diseases in Dogs. Full Prescribing Information" (PDF) (in Russian). Sanofi Russia. Archived from the original (PDF) on 13 July 2018. Retrieved 14 November 2016.
  5. 1 2 Papich, Mark (2016). Saunders Handbook of Veterinary Drugs (4th ed.). Elsevier. ISBN   978-0-323-24485-5.
  6. ↑ 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. PMID   25688713.
  7. ↑ 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. PMID   9416671. S2CID   5028039.
  8. ↑ "CVMP assessment report for Nexgard (EMEA/V/C/002729/0000)" (PDF). European Medicines Agency. Retrieved 14 November 2019.
  9. 1 2 "Nexgard Spectra EPAR". European Medicines Agency. 10 February 2015. Retrieved 16 June 2024.
  10. ↑ "CVMP Assessment Report for Nexgard Spectra (EMEA/V/C/003842/0000)" (PDF). European Medicines Agency. Retrieved 14 November 2019.
  11. ↑ Shoop WL, Hartline EJ, Gould BR, Waddell ME, McDowell RG, Kinney JB, et al. (April 2014). "Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs". Veterinary Parasitology. 201 (3–4): 179–189. doi: 10.1016/j.vetpar.2014.02.020 . PMID   24631502.
  12. ↑ Beugnet F, deVos C, Liebenberg J, Halos L, Fourie J (25 August 2014). "Afoxolaner against fleas: immediate efficacy and resultant mortality after short exposure on dogs". Parasite. 21: 42. doi:10.1051/parasite/2014045. PMC   4141545 . PMID   25148564.
  13. ↑ Beugnet F, Crafford D, de Vos C, Kok D, Larsen D, Fourie J (August 2016). "Evaluation of the efficacy of monthly oral administration of afoxolaner plus milbemycin oxime (Nexgard Spectra, Merial) in the prevention of adult Spirocerca lupi establishment in experimentally infected dogs". Veterinary Parasitology. 226: 150–161. doi: 10.1016/j.vetpar.2016.07.002 . PMID   27514901.
  14. ↑ "Boehringer-Ingelheim companion-animals-product Nexgard (afoxolaner)". Boehringer Ingelheim International GmbH. Retrieved 13 November 2019.
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