The Metabolism of Chlorpromazine and Promethazine to give New ‘Pink Spots’

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Abstract
1. The ‘pink spots’ observed in the in vivo and in vitro metabolism of chlorpromazine and promethazine were identified as N-oxidation products of 2-chlorophenothiazine and phenothiazine, respectively. 2. Incubations of the latter two compounds with fortified hepatic fractions from rabbit and guinea-pig gave the corresponding hydroxylamines, the nitroxides which were purplish-pink and gave characteristic e.s.r. signals, and the N-hydroperoxides which were the major pink compounds and gave no e.s.r. signals. Each hydroxylamine was readily oxidized to an N-hydroperoxide in air and the latter readily reduced back in solution to the corresponding hydroxylamine by ascorbic acid. 3. The synthesis, chemical properties and the i.r., u.v., n.m.r., e.s.r., and mass spectra of the above compounds, their sulphoxides and phenothiazine-N-peroxides are reported.