Abstract
The fate of 10-(1-methyl-3-pyrrolidyl methyl) phenothiazine hydrochloride (methdilazine) in the organism was studied in mice, rats, and guinea pigs. It was absorbed rather slowly from the stomach and very rapidly from the small intestine. Approximately one-fourth of an oral or subcutaneous dose was excreted in the urine of mice and rats, and approximately 15% of an oral dose was found in the urine of guinea pigs. The drug was excreted chiefly as a metabolite which was probably the sulfoxide of methdilazine. This antihistaminic agent was distributed throughout the body, but was less concentrated in the brain than are two similar phenothiazine derivatives. There was no residual methdilazine in the tissues examined 24 hours after a single administraticn, ncr was there any accumulation after repeated daily doses. Methdilazine had a relatively low acute toxicity potential in rats, mice, guinea pigs, rabbits, and dogs. Chronic administration of daily doses of 9.5, 19, 38, and 75 mg/kg to rats and 1, 2, and 3 mg/kg to dogs showed no toxic effects which could be attributed to the drug.
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