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Table 3 Major classes of anthelmintics used for the treatment of nematode infections in livestock; their mode of action (if known) and proposed mechanisms of resistance

From: Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective

Anthelmintic class Understood mode of action Proposed mechanisms of resistance Reference
Benzimidazoles Bind to β-tubulin and prevent the formation of microtubules. Causes the inhibition of glucose uptake, protein secretion and microtubule production, leading to starvation of the parasite. Mutations in the β-tubulin gene, causing structural changes in β-tubulin. As a consequence, the drug can no longer bind to its target site. [9496]
Imidazothiazoles/tetrahydropyrimidines Mimic the action of acetylcholine causing spastic paralysis of the worms. Paralyzed worms are expelled by normal gut peristalsis, leading to rapid removal of present worms. Poorly understood; possible involvement of structual changes in the nicotinic acetylcholine receptor, preventing the binding of the drug. Also proposed have been changes in the sensitivity of the receptor towards acetylcholine, which can lead to a cross-resistance with organophosphates. [97100]
Macrocyclic lactones (avermectins/milbemycins) Causes an opening of glutamate-gated chloride channels (GluCI). This leads to an increased CI-ion influx into nerve cell, causing flaccid paralysis of the worm. Poorly understood; possible involvement of: mutations in P-glycoprotein gene could cause a gain-of-function, leading to a more rapid removal of the drug from the parasite. Selection at glutamate- and γ-aminobutyric-acid gated chloride channels. [101103]
Amino-acetonitrile derivatives The hypothesized mode of action involves a nematode-specific clade of acetylcholine receptor subunits. Full or partial loss of the gene which encodes the particular type of acetylcholine receptor. [56]