Lack of correlation between schistosomicidal and anticholinergic properties of hycanthone and related drugs.
Visual observation of the motor activity of Schistosoma mansoni kept in vitro showed an increase of activity in the presence of hycanthone (HC). In addition, HC caused a delay in the paralytic effects of carbachol. Similar results were observed in the presence of oxamniquine (OXA). The same pattern of motor activity, however, was shown by HC-resistant worms, by Schistosoma japonicum, and by worms exposed to drug precursors (lucanthone and UK-3883), which are not schistosomicidal in vitro. Other analogs with in vitro killing activity (IA-4 and IA-4 N-oxide) showed minimal anticholinergic effects. The anticholinergic effects of HC and OXA were quickly reversible in vitro and in vivo, whereas their antischistosomal effects are irreversible and delayed. Incubation of schistosomes with high concentrations of carbachol or with anticholinergic drugs failed to compete with the schistosomicidal effects of HC. These results are viewed as contradictory to the hypothesis that HC kills schistosomes by blocking their acetylcholine receptors.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006826:Hycanthone / Q000494:pharmacology*; D008154:Lucanthone / Q000494:pharmacology; D008297:Male; D009068:Movement / Q000187:drug effects; D009600:Nitroquinolines / Q000494:pharmacology*; D010073:Oxamniquine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000502:physiology; D013892:Thioxanthenes / Q000494:pharmacology*
D009600:Nitroquinolines; D010276:Parasympatholytics; D013892:Thioxanthenes; D010073:Oxamniquine; C001484:desoxyoxamniquine; D006826:Hycanthone; D002217:Carbachol; D008154:Lucanthone