Add time:08/12/2019         Source:sciencedirect.com

The acute toxicity of a candidate antimalarial drug, 4-fluoro-4′-trifluoromethyl benzophenone guanylhydrazone hydrochloride (FTBG; WR 09792), was measured by intraperitoneal and oral administration to mice, rats, and guinea pigs. The LD50 values were between 11.5 and 27.9 mg/kg by the intraperitoneal route and between 114 and 199 mg/kg by the oral route. Subacute oral toxicity measurements demonstrated that a daily dose of 5 mg/kg was the highest dose that could be tolerated for 14 days without mortality or a decrease in leukocytes. Measurements of the effects of FTBG on hepatic microsomal enzymes demonstrated that this compound produces a marked and specific increase in the O-demethylase activity of the livers of rats when repeated daily doses are given intraperitoneally or orally. No induction of the other microsomal enzymes that were measured was noted, and induction of O-demethylase did not occur in mice and guinea pigs. Reversible, dose-related increases in O-demethylase activity occurred with 1 mg/kg and higher doses of FTBG daily for 5 days. Examination of structurally related compounds indicated that the trifluoromethyl substituent of FTBG is involved in the induction of O-demethylase activity.

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