Cited by 439Helminth infection and controlVeterinary Pharmacology and AnesthesiaInsect Resistance and Genetics

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Moxidectin and the avermectins: Consanguinity but not identity

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Prichard, Roger, Ménez, Cécile, Lespine, Anne·2012·International Journal for Parasitology: Drugs and Drug Resistance

DOI 10.1016/j.ijpddr.2012.04.001PMC PMC3862425

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Abstract

• Avermectins and moxidectin have a macrocyclic lactone ring but different substituents. • They differ in terms of physicochemical properties, pharmacodynamics and kinetics. • They act on ligand-gated anion channels of invertebrates but with binding differences. • They interact differently with ABC transporters affecting toxicity. • In nematodes, this may explain different abilities to induce anthelmintic resistance. The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination.

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Authors: Prichard, R., Ménez, C., & Lespine, A.
Affiliations: McGill University (CA)
Université Toulouse III - Paul Sabatier (FR)
Corresponding author: Lespine, Anne
ORCID: Prichard, Roger
Lespine, Anne
Venue: International Journal for Parasitology: Drugs and Drug Resistance
Publisher: Elsevier BV
Published: 2012-12
Volume: 2
Pages: 134-153
ISSN: 2211-3207 (ISSN-L)
DOI: 10.1016/j.ijpddr.2012.04.001
PMC: PMC3862425
OpenAlex: W2015519080
Cited by: 439
References: 210
Citations by year: 2026: 13 · 2025: 25 · 2024: 12 · 2023: 30 · 2022: 34 · 2021: 35 · 2020: 35 · 2019: 25 · 2018: 37 · 2017: 17 · 2016: 26 · 2015: 26 · 2014: 14 · 2013: 15 · 2012: 12
FWCI: 4.90
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor, 227 d)
Locations: International Journal for Parasitology Drugs and Drug Resistance (publishedVersion, cc-by-nc-nd)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, cc-by)
Funders: McGill University
Ministère de l'Agriculture, des Pêcheries et de l'Alimentation
Wellcome Trust
Agence Nationale de la Recherche
Fonds Québécois de la Recherche sur la Nature et les Technologies
Institut National de la Recherche Agronomique
Natural Sciences and Engineering Research Council of Canada
Topics: Life Sciences › Immunology and Microbiology › Parasitology › Helminth infection and control
Health Sciences › Veterinary › Small Animals › Veterinary Pharmacology and Anesthesia
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Insect Resistance and Genetics
Keywords: moxidectin, avermectin, milbemycins, macrocyclic lactones, anthelmintic resistance, cross-resistance, ligand-gated ion channels, ABC transporters, glutamate-gated ion channels, pharmacokinetics, toxicity, nematodes, arthropods, anthelmintic formulations

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Moxidectin and the avermectins: Consanguinity but not identity

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