Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes.

摘要: The control of parasitic nematodes impacting animal health relies on the use broad spectrum anthelmintics. However, intensive these drugs has led to selection resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able parasites. Nicotine also historically been used as a de-wormer but was removed from market when modern anthelmintics became available. pharmacological target nicotine identified acetylcholine-gated ion channels. Nicotinic-sensitive acetylcholine receptors (N-AChRs) therefore represent validated targets remain largely under-exploited. present study, using automated larval migration assay (ALMA), we report nicotinic derivatives efficiently paralyzed multiple (benzimidazoles/levamisole/pyrantel/ivermectin) field isolate H. contortus. Using C. elegans model confirmed N-AChRs are preferential nornicotine and anabasine. Functional expression homomeric N-AChR distantly related horse parasite Parascaris equorum Xenopus oocytes highlighted some striking differences their respective properties towards derivative sensitivity. This work validates exploitation development resistance-breaking compounds.