Efficacy of Amoscanate against Experimental Schistosomal Infections in Monkeys

Karen A. CrawfordCenter for Tropical Diseases, University of Lowell, Department of Immunology and Infectious Diseases, Johns Hopkins Medical School, Department of Pharmacology, University of Massachusetts Medical School, Lowell, Massachusetts 01854

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Harold L. AschCenter for Tropical Diseases, University of Lowell, Department of Immunology and Infectious Diseases, Johns Hopkins Medical School, Department of Pharmacology, University of Massachusetts Medical School, Lowell, Massachusetts 01854

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John I. BruceCenter for Tropical Diseases, University of Lowell, Department of Immunology and Infectious Diseases, Johns Hopkins Medical School, Department of Pharmacology, University of Massachusetts Medical School, Lowell, Massachusetts 01854

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Ernest BuedingCenter for Tropical Diseases, University of Lowell, Department of Immunology and Infectious Diseases, Johns Hopkins Medical School, Department of Pharmacology, University of Massachusetts Medical School, Lowell, Massachusetts 01854

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Emil R. SmithCenter for Tropical Diseases, University of Lowell, Department of Immunology and Infectious Diseases, Johns Hopkins Medical School, Department of Pharmacology, University of Massachusetts Medical School, Lowell, Massachusetts 01854

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The antischistosomal activity of oral doses of amoscanate (4-isothiocyanato-4′-nitrodiphenylamine) was determined in infected Cebus apella (capuchin monkeys) and Macaca mulatta (rhesus monkeys). In C. apella infected with Schistosoma japonicum or S. mansoni an initial dose of 10 mg/kg body weight did not alter fecal egg counts, but a subsequent dose of 25 mg/kg markedly reduced both egg counts and worm burdens; in animals infected with S. haematobium, a single dose of 25 mg/kg of amoscanate was similarly effective. Comparable schistosomicidal effects were also produced in S. japonicum- and S. mansoni-infected M. mulatta by single oral doses of 20 and 35 mg/kg, respectively. In both C. apella and M. mulatta the coadministration of single oral doses of 50 or 75 mg/kg of erythromycin attenuated the appearance of mutagenic metabolites of amoscanate in the urine but did not interfere with the antischistosomal action of amoscanate. In non-infected monkeys single oral doses of 75 mg/kg of amoscanate with or without erythromycin (50 mg/kg in C. apella or 75 mg/kg in M. mulatta) did not cause any major organ toxicity as revealed by gross and histopathologic examination, hematology, blood chemistry, electrocardiograms and urinalysis. The data indicate that in C. apella and M. mulatta, amoscanate is a relatively non-toxic antischistosomal agent effective orally against a broad spectrum of schistosome species.

Author Notes

Present address: Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, New York 14263.

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