The
cholinergic class of
anthelmintic drugs is used for the control of parasitic nematodes. One of this class of drugs,
tribendimidine (a symmetrical
diamidine derivative, of
amidantel), was developed in China for use in humans in the mid-1980s. It has a broader-spectrum
anthelmintic action against soil-transmitted
helminthiasis than other
cholinergic anthelmintics, and is effective against hookworm, pinworms, roundworms, and Strongyloides and flatworm of humans. Although molecular studies on C. elegans suggest that
tribendimidine is a
cholinergic agonist that is selective for the same nematode muscle nAChR as
levamisole, no direct electrophysiological observations in nematode parasites have been made to test this hypothesis. Also the hypothesis that
levamisole and tribendimine act on the same receptor, does not explain why
tribendimidine is effective against some nematode parasites when
levamisole is not. Here we examine the effects of
tribendimidine on the electrophysiology and contraction of Ascaris suum body muscle and show that
tribendimidine produces depolarization antagonized by the nicotinic antagonist
mecamylamine, and that
tribendimidine is an agonist of muscle nAChRs of parasitic nematodes. Further pharmacological characterization of the nAChRs activated by
tribendimidine in our Ascaris muscle contraction assay shows that
tribendimidine is not selective for the same receptor subtypes as
levamisole, and that
tribendimidine is more selective for the B-subtype than the L-subtype of nAChR. In addition, larval migration inhibition assays with
levamisole-resistant Oesophagostomum dentatum isolates show that
tribendimidine is as active on a
levamisole-resistant isolate as on a
levamisole-sensitive isolate, suggesting that the selectivity for
levamisole and
tribendimidine is not the same. It is concluded that
tribendimidine can activate a different population of nematode parasite nAChRs than
levamisole, and is more like bephenium. The different nAChR subtype selectivity of
tribendimidine may explain why the spectrum of action of
tribendimidine is different to that of other
cholinergic anthelmintics like
levamisole.