The Mode of Action of Phenothiazine As an Anthelmintic II. Phenothiazine in the Intestinal Fluid and Nematode Parasites of Treated Animals

Abstract

SummaryMethods are described for the identification of phenothiazine and its oxidation products by paper chromatography and by microionophoresis with the use of 35S-labelled phenothiazine.Extracts of the intestinal fluid from rats and chickens dosed with the drug were analysed for the presence of phenothiazine and its derivatives by these techniques. Only phenothiazine was detected in the intestinal fluid of either host but it appeared to be attached to a fatty substance from which it could not be separated by acid or alkaline hydrolysis. This phenothiazin~fat complex was not formed under anaerobic conditions in vitro; again, no oxidation products of the drug were detected but only phenothiazine was identified.When Ascaridia galli was exposed to radioactive phenothiazine in vivo,. 10 per cent. of the 35S recovered was found in the acid-soluble fraction of the tissues and 68 per cent. in the alcohol-soluble fraction.The parasites also appeared to contain the fatty complex of phenothiazine, and oxidation products of the drug could not be detected. The phenothiazine complex found i~ extracts of the gut fluid of the chicken penetrated in vitro the tissues of Ascaridia galli at a slower rate than did a suspension of the pure drug.The results of the investigation indicate that phenothiazine itself, not its oxidation derivatives, is the anthelmintic agent.