Schistosoma mansoni: Species-selective response to N-chloroethyl-acetylcholine derivatives

• Published in: Experimental parasitology Vol. 56; no. 1; pp. 70 - 80
• Main Authors: Willcockson, Wm.S., Ahmed, Ahmed E., Hillman, Gilbert R.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.01.1983; Elsevier
• Subjects: Acetylcholine - analogs & derivatives; Acetylcholine - pharmacology; Acetylcholine mustard analogs; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Blood fluke; Carbachol - pharmacology; Diseases caused by trematodes; Dose-Response Relationship, Drug; drugs; Frog rectus abdominus; Guinea pig ileum; Guinea Pigs; Helminthic diseases; Histamine - pharmacology; Infectious diseases; mechanism of action; Medical sciences; Movement - drug effects; Neuromuscular Junction - drug effects; Parasitic diseases; pharmacology; Pharmacology. Drug treatments; Pilocarpine - pharmacology; Ranidae; Schistosoma mansoni; Schistosoma mansoni - drug effects; Schistosoma mansoni - physiology; Schistosomiases; Serotonin - pharmacology; Species Specificity; Structure-Activity Relationship; Trematode; Tropical medicine; Guinea pig ileum; Schistosoma mansoni; Frog rectus abdominus; Blood fluke; Trematode; Acetylcholine mustard analogs; Helmintha; Plathelmintha; Anthelmintic; Sensitivity resistance; Invertebrata
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/0014-4894(83)90097-8

Three new acetylcholine mustard analogs were tested on schislosome and vertebrate neuromuscular preparations. These compounds extend a previously reported structure-activity series. The new compounds investigated include isopropyl-, cyclohexyl-, and benzyl-2-acetoxyethyl-2′-chloroethylamine (PrM, ChM, and BzM). In schistosome motor activity studies, all of the compounds caused irreversible reductions in the activity of Schistosoma mansoni after 1 hr exposure followed by 19 hr in drug-free medium. Under nonlethal conditions of dosage and exposure time, all compounds blocked carbachol-induced paralysis, indicating a possible action at schistosome cholinergic sites. All the compounds also reduced the labeling of schistosomes by dimethylaminonapthalene-5-sulfonamidoethyl dimethylamine hydrochloride (DDNS), a fluorescent ACh analog. In isolated vertebrate tissue experiments, PrM and ChM had slight agonist activity in the guinea pig ileum, and only PrM had agonist activity in the frog rectus abdominis preparation. PrM and BzM were found to antagonize ACh responses in the guinea pig ileum. Exposure of vertebrate tissues for 1 hr to high concentrations of ChM caused no long-lasting inhibition of ACh, pilocarpine, and serotonin (5HT) responses. Histamine responses were slightly reduced from control. Following 1 hr exposure of vertebrate tissues to PrM, initial reductions in all responses were seen, followed by recoveries to near control. BzM treatment, however, reduced all responses far below control; the tissues did not recover even after washing for 2 hr. It is concluded that ChM and, to a lesser extent, PrM, had a greater effect on schistosomes than on vertebrate tissues. BzM did not display species selectivity in this favorable direction.