Effects of acetylcholine mustard analogs on schistosome and vertebrate neuromuscular preparations.

Two acetylcholine mustard analogs were synthesized for studies of the structural requirements for drugs having selective neurotoxic effects in schistosomes. Drugs investigated in the present study include methyl- and butyl-2-acetoxyethyl-2'-chloroethylamine (MeM and BuM). In worm activity monitor experiments, both MeM and BuM irreversibly paralyzed Schistosoma mansoni after 1-hr exposure followed by 19 hr in drug-free medium. The concentrations required for parasite paralysis were similar to effective concentrations of known antischistosomal drugs. An immediate effect of both compounds was blockage of carbachol-induced paralysis, suggesting that they may bind at schistosome cholinergic sites. Furthermore, fluorescent labeling of schistosomes with dansyl choline was reduced by both compounds. In vertebrate studies, while MeM was a potent agonist at both muscarinic and nicotinic receptors, BuM had only a slight effect. MeM and BuM had no major irreversible cholinergic effect in vertebrate tissues. BuM, therefore, has distinctly different pharmacological actions in schistosomes and in vertebrates.