STUDIES ON THE ANTISCHISTOSOMAL ACTION AND TOXICITY OF PHENYL 4-NITRO-DIPHENYLAMINO 4'-THIONCARBAMATE (7720)

The antischistosomal action and toxicity of phenyl-4-nitrodiphenylamino-4'-thioncarbamate (7720), a new compound related to Amoscanate (C9333-Go/CGP4540),were studied. The results of our experiments showed that 7720 exhibited a dramatic curative effect as C9333 on experimental schistosomiasis. The 50% curative dose (CD₅₀) of 7720 and C9333 given intragastrically in mice against S. japonicum was 79.0 μmol/kg/day (or 28.8 mg/kg/day)×5 and 83.4 μmol/kg/day (or 22.6 mg/kg/day)×5, respectively. The rabbits infected with S. japonicum were free from worms of both sexes after treatment with 7720 by dosage regimes of either 16 or 32 mg/kg/day for 5 consecutive days. 7720 was tolerated asymptomatically by mice in a single oral dose of 5 g/kg. The results obtained by the oral subacute toxicity test on dogs and rats, including observation of the effect on the body weight growth rate of young rats, liver function and renal function tests, hematological routine test, EKG as well as histopathological examination showed that 7720 displayed few toxic actions. The therapeutic effect of Lopatol, a diphenyl ether analogue of C9333, was also studied in rabbits infected with S. japonicum. All the rabbits treated with Lopatol were completely cured by a dosage regime of 40 mg/kg/day×5, intragastrically.