Biotransformations in vitro undergone by phenothiazine derivatives in a liver preparation

Abstract

Characterisation of the products of biotransformations resulting when a wide range of medicinally used phenothiazine derivatives were incubated with a “microsomal and soluble” fraction of livers from albino Wistar rats, is described. The compounds were chlorpromazine, demethylchlorpromazine, dedimethylchlorpromazine, triflupromazine, promazine, acepromazine, propiomazine, diethazine, promethazine, isopromethazine, ethopropazine, trimeprazine, methotrimeprazine, ethylmemazine, proquamezine, cyamemazine, trifluoperazine, prochlorperazine, thioproperazine, fluphenazine, pecazine, and also the sulphoxides of the first three compounds and of promazine. The predominant reactions were those of dealkylation and of hydroxylation of the aromatic ring. Sulphoxidation did not occur to a significant extent with any of the compounds examined.