title: Effects of acetylcholine mustard analogs on schistosome and vertebrate neuromuscular preparations.
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.
mesh_terms: D000109:Acetylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001001:Anura; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009068:Movement / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D010276:Parasympatholytics; D012550:Schistosoma mansoni / Q000187:drug effects; D012556:Schistosomicides
chemical_list: D010276:Parasympatholytics; D012556:Schistosomicides; C002561:acetylcholine mustard; D000109:Acetylcholine