title: Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin.
abstract: Studies were conducted to determine whether organisms which are resistant to ivermectin are also resistant to moxidectin. The mechanisms of action of moxidectin and ivermectin were compared by measuring the changes in membrane conductance they induced in leg muscle fibres of the common shore crab (Pachygrapsus crassipes) by using standard micro-electrode techniques. Meriones unguiculatus (jirds) were infected with ivermectin-resistant or -susceptible strains of Haemonchus contortus, treated with moxidectin or ivermectin at a dose which routinely clears more than 98 per cent of the susceptible strain, and examined for parasite clearance. The results showed that moxidectin induced a rapid loss of membrane resistance in the muscle preparation, and that the effect was almost 50 per cent reversible with the chloride channel-blocker picrotoxinin; this pattern of activity is qualitatively similar to that of ivermectin. In the jird model, moxidectin achieved a clearance of only < or = 47.2 per cent against ivermectin-resistant H contortus at a dose which invariably clears > or = 98 per cent of an ivermectin-susceptible strain. These results indicate that moxidectin and ivermectin share a common mechanism of action, and that organisms that are resistant to ivermectin are also likely to be resistant to moxidectin.
authors.affiliation: Animal Health Therapeutics, Upjohn Laboratories, Kalamazoo, Michigan 49001.
authors.forename: G A
authors.initials: GA
authors.lastname: Conder
authors.forename: D P
authors.initials: DP
authors.lastname: Thompson
authors.forename: S S
authors.initials: SS
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003386:Brachyura; D004351:Drug Resistance; D005260:Female; D005849:Gerbillinae; D006188:Haemonchiasis / Q000188:drug therapy; D006189:Haemonchus / Q000187:drug effects*; D007559:Ivermectin / Q000494:pharmacology*; D018942:Macrolides; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010852:Picrotoxin / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D007559:Ivermectin; D018942:Macrolides; D010852:Picrotoxin; C027837:moxidectin