EFFECTS OF ACETYLCHOLINE MUSTARD ANALOGS ON SCHISTOSOME AND VERTEBRATE NEUROMUSCULAR PREPARATIONS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 218  (2) , 330-336
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, MeM and BuM irreversibly paralyzed Schistosoma mansoni after 1-h exposure followed by 19 h 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. Fluorescent labeling of schistosomes with dansyl choline was reduced by both compounds. In vertebrate studies, while MeM was a potent agonist at muscarinic and nicotinic receptors, BuM had only a slight effect. MeM and BuM had no major irreversible cholinergic effect in vertebrate tissues. BuM has distinctly different pharmacological actions in schistosomes and in vertebrates.