Anticholinergic properties of the antischistosomal drug hycanthone.

The American Journal of Tropical Medicine and Hygiene
G R Hillman, A W Senft

Abstract

The effect of the antischistosomal drug hycanthone on the motor activity of Schistosoma mansoni was studied in vitro. Hycanthone stimulates motor activity at concentrations of 10(-6) to 10(-5) M, and partially blocks the paralytic effects of carbachol and physostigmine. Lucanthone, a closely related although less active congener of hycanthone, does not produce these same effects in vitro. Some blocking of acetylcholine can also be produced by atropine, although this drug is less active in this regard than is hycanthone. These findings suggest that the therapeutic efficacy of hycanthone may be related to interference with acetylcholine receptors in schistosomes. Hycanthone is an inhibitor of acetylcholinesterase (ACHE) from S. mansoni, but is less effective against ACHE of mammalian origin. In contrast, physostigmine inhibits the mammalian enzyme more effectively than it does the helminth enzyme. These observations suggest that schistosome ACHE differs from the mammalian enzyme with respect to the configuration of the active center, and that hycanthone may have a selective affinity for schistosomal cholinergic systems.

Citations

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