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Excretion Patterns of Phenothiazine-S35 Compounds in Rats

1962; Elsevier BV; Volume: 51; Issue: 10 Linguagem: Inglês

10.1002/jps.2600511021

1520-6017

Thomas L. Flanagan, Jack Newman, Alfred R. Maass, Edward J. Van Loon,

Synthesis and Reactivity of Heterocycles

The excretion patterns of five S35-labeled phenothiazines were compared in rats following the oral administration of pharmacologically active doses. Substitution in the 2 position in the phenothiazine ring did not have any apparent effect upon the S35 excretion pattern. Differences in the structure of the side chain did have an effect upon the mode of S35 excretion. The urinary S35 excretion decreased and the fecal S35 excretion correspondingly increased as the side-chain structure was changed from 3-dimethylaminopropyl to 3-dimethylamino-2-methylpropyl to 4-methyl-1-piperazinylpropyl. At a dosage level of 9.0 mg. of free base/Kg. in rats, the urinary S35 excretion following the oral administration of compound II [2-chloro-10-(3-dimethylaminopropyl) phenothiazine-S35 hydrochloride] was twice as great as the urinary S35 excretion following the oral administration of compound III [10-[3- (4-methyl-1-piperazinyl)-propyl]-2-trifluoromethylphenothiazine-S35 dihydrochloride]. The former compound contained a chlorine atom in the 2 position of the phenothiazine nucleus, while the latter contained a trifluoromethyl grouping at this position. The increased dosage level (9.0 mg. of free base/Kg.) did not appreciably change the S35 excretion pattern of compound IV [10-(3-dimethyl-amino-2-methylpropyl)phenothiazine-S35 tartrate] and compound V [10-(3-dimethylamino-2-methylpropyl)-2-trifluoromethylphenothiazine-S35 hydrochloride].