Moxidectin

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Moxidectin
Structural formula of moxidectin
Ball-and-stick model of the moxidectin molecule
Clinical data
Trade names Cydectin, Equest, ProHeart, Quest.[1]
Synonyms CL 301,423;[2] milbemycin B.[2]
AHFS/Drugs.com International Drug Names
Routes of
administration
oral, topical, subcutaneous
ATCvet code
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ECHA InfoCard 100.163.046 Edit this at Wikidata
Chemical and physical data
Formula C37H53NO8
Molar mass 639.819 g/mol
3D model (JSmol)
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Moxidectin is an anthelmintic drug used in animals to prevent or control parasitic worms (helminths), such as heartworm and intestinal worms, in dogs, cats, horses, cattle and sheep. Moxidectin kills some of the most common internal and external parasites by selectively binding to a parasite's glutamate-gated chloride ion channels. These channels are vital to the function of invertebrate nerve and muscle cells; when moxidectin binds to the channels, it disrupts neurotransmission, resulting in paralysis and death of the parasite.

Medicinal uses[edit]

Nematodes can develop cross-resistance between moxidectin and other similar parasiticides, such as ivermectin, doramectin and abamectin.[6]

Adverse effects[edit]

Studies of moxidectin show the side effects vary by animal and may be affected by the product’s formulation, application method and dosage.

An overdose of moxidectin enhances the effect of gamma-aminobutyric acid (GABA) in the central nervous system.[7] In horses, overdose may lead to depression, drooping of the lower lip, tremor, lack of coordination when moving (ataxia), decreased rate of breathing (respiratory rate), stupor and coma.[7]

If a dog licks moxidectin from the skin which was applied as a "spot-on" (topical) treatment, this has the same effect as an overdose, and may cause vomiting, salivation and neurological signs such as ataxia, tremor, and nystagmus.[3] Collie dogs cannot be administered moxidectin.[3]

Pharmacology[edit]

Moxidectin is very lipophilic, which causes it to have a high volume of distribution.[8] Moxidectin concentrates in the animal's adipose tissue, from where it is released for up to two months following administration.[8]

In goats, the oral bioavailability of moxidectin is 2.7 times lower, and the half-life is 1.8 times shorter than in sheep.[9]

Chemistry[edit]

Moxidectin, a macrocyclic lactone of the milbemycin class,[3] is a semisynthetic derivative of nemadectin, which is a fermentation product of the bacterium Streptomyces cyanogriseus subsp. noncyanogenus.[10]

History[edit]

In the late 1980s, an American Cyanamid Company agronomist discovered the Streptomyces bacteria from which moxidectin is derived in a soil sample from Australia. Two companies filed patents for moxidectin: Glaxo Group and the American Cyanamid Company;[1] in 1988, all patents were transferred to American Cyanamid.[1] In 1990, the first moxidectin product was sold in Argentina.[1]

Use in humans[edit]

Moxidectin has been approved by US FDA for the treatment of onchocerciasis (river-blindness) in people aged 12 years of age and older on the basis of two clinical trials.[11] Moxidectin is predicted to be a helpful tool to achieve elimination goals of this disease.[12] The license holder is the nonprofit biopharmaceutical company Medicines Development for Global Health.

References[edit]

  1. ^ a b c d e Awasthi, A; Razzak, M; Al-Kassas, R; Harvey, J; Garg, S (2013). "Chapter 7: Analytical profile of moxidectin". In Brittain, Harry. Profiles of drug substances, excipients and related methodology: Volume 38. Amsterdam: Academic Press. pp. 315–366. ISBN 9780124078284. 
  2. ^ a b "milbemycin". MeSH - NCBI. Retrieved 2017-07-21. 
  3. ^ a b c d Patel, A; Forsythe, P (2008). Small animal dermatology. Edinburgh: Elsevier/Saunders. p. 26. ISBN 9780702028700. 
  4. ^ Papich, Mark G. (2011). "Moxidectin". Saunders handbook of veterinary drugs small and large animal (3rd ed.). Philadelphia, PA: Elsevier/Saunders. pp. 525–526. ISBN 9781437701920. 
  5. ^ Sargison, Neil (2008). "Moxidectin". Sheep flock health a planned approach. Oxford: Blackwell Publishing. pp. 180–181. ISBN 9781444302608. 
  6. ^ Rugg, D; Buckingham, SD; Sattelle, DB; Jansson, RK (2010). "The insecticidal macrocyclic lactones". In Gilbert, GI; Gill, SS. Insect pharmacology channels, receptors, toxins and enzymes. London: Academic Press. ISBN 9780123814487. 
  7. ^ a b Dowling, PM (2012). "Ivermectin and moxidectin toxicosis". In Wilson, DA. Clinical veterinary advisor: The horse. St. Louis, MO: Elsevier Saunders. pp. 307–308. ISBN 9781437714494. 
  8. ^ a b Lanusse, CE; Lifschitz, AL; Imperiale, FA (2013). "Chapter 42: Macrocyclic lactones: Endectocide compounds". In Riviere, JE; Papich, MG. Veterinary Pharmacology and Therapeutics (9th ed.). John Wiley & Sons. p. 1126. ISBN 1118685903. 
  9. ^ Baynes, RE; Payne, M; Martin-Jimenez, T; Abdullah, AR; Anderson, KL; Webb, AI; Craigmill, A; Riviere, JE (1 September 2000). "Extralabel use of ivermectin and moxidectin in food animals". Journal of the American Veterinary Medical Association. 217 (5): 668–71. doi:10.2460/javma.2000.217.668. PMID 10976297. 
  10. ^ Lumaret, JP; Errouissi, F; Floate, K; Römbke, J; Wardhaugh, K (May 2012). "A review on the toxicity and non-target effects of macrocyclic lactones in terrestrial and aquatic environments". Current pharmaceutical biotechnology. 13 (6): 1004–60. PMC 3409360Freely accessible. PMID 22039795. 
  11. ^ Awadzi, K; Opoku, NO; Attah, SK; Lazdins-Helds, J; Kuesel, AC (June 2014). "A randomized, single-ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection". PLOS Neglected Tropical Diseases. 8 (6): e2953. doi:10.1371/journal.pntd.0002953. PMC 4072596Freely accessible. PMID 24968000. 
  12. ^ Turner, HC; Walker, M; Attah, SK; Opoku, NO; Awadzi, K; Kuesel, AC; Basáñez, MG (19 March 2015). "The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data". Parasites & Vectors. 8: 167. doi:10.1186/s13071-015-0779-4. PMC 4381491Freely accessible. PMID 25889256.