Table 4.3.
Main anthelmintics used for the treatment of nematode infections in livestock; their mode of action (if known) and proposed mechanisms of resistance
| Anthelmintics | Understood mode of action | Proposed mechanisms of resistance | References |
|---|---|---|---|
| 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. |
Lacey (1988) Winterrowd et al. (2003) |
| Imidazothiazoles/tetrahydropyrimidines | Mimic the action of acetylcholine causing spastic paralysis of the worms. Paralysed worms are expelled by normal gut peristalsis leading to rapid removal of present worms. |
Poorly understood, possible involvement of structural 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. |
Richmond and Jorgensen (1999) Robertson et al. (1999) Martin et al. (2003) Martin and Robertson (2007) |
| Macrocyclic lactones (avermectins/milbemycins) | Causes an opening of glutamate-gated chloride channels (GluCl). This leads to an increased C1− 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 y-aminobutyric-acid-gated chloride channels. |
Blackhall et al. (1998) Blackhall et al. (2003) Kerboeuf et al. (2003) |
| 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. | Kaminsky et al. (2008) |
| Cycloocta-depsipeptides (emodepside/PFIO22A) | Binds to a presynaptic latrophilin receptor in nematodes. |
Harder et al. (2003) Harder et al. (2005) von Samson-Himmelstjerna et al. (2005) |
|