The interactions of anthelmintic drugs with nicotinic receptors in parasitic nematodes

Abstract

Parasitic nematodes express a large number of distinct nicotinic acetylcholine receptors and these in turn are the targets of many classes of anthelmintic drug. This complexity poses many challenges to the field, including sorting the exact subunit composition of each of the receptor subtypes and how much they vary between species. It is clear that the model organism Caenorhabditis elegans does not recapitulate the complexity of nicotinic pharmacology of many parasite species and data using this system may be misleading when applied to them. The number of different receptors may allow nematodes some plasticity which they can exploit to evolve resistance to a specific cholinergic drug; however, this may mean that combinations of cholinergic agents may be effective at sustainably controlling them. Resistance may involve the expression of truncated receptor subunits that affect the expression levels of the receptors via mechanisms that remain to be deciphered.