The avermectin/milbemycin class of anthelmintics, exemplified by ivermectin, has a massive impact on human and animal diseases caused by parasitic nematodes. This success has been somewhat overshadowed, at least in animal health, by the emergence of drug resistance in many species. The anthelmintic action of ivermectin is due to its action at glutamate-gated chloride channels (GluCls), inhibitor members of the pentameric ligand-gated ion channel family of receptors. Ivermectin can interact with many other molecular targets but none have so far been shown to modulate its antiparasitic activity. GluCl are widely expressed in the nematode nervous system and mediate many physiological processes, including locomotion, sensory perception, reproduction, feeding and secretion. The channel subunits are encoded by a group of up to 8 genes, the composition of which varies between species. Nematodes thus have the capacity to encode a wide variety of GluCls, and the subunit composition of the native channels remains obscure, though some success has been reported in the co-expression of certain subunits in heterologous systems. For example, GLC-2 and GLC-3 can be co-expressed in <i>Xenopus </i>oocytes to form a novel GluCl subtype sensitive to ivermectin, and in at <i>Parascaris</i> AVR-14B can also co-assemble with GLC-2 to form a novel channel.

Avermectin targets in parasitic nematodes

ACS Fall 2021

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