Abstract

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.