Metabolism of the phenothiazine drug perazine by liver and lung microsomes from various species

  • Breyer U
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The oxidative metabolism of perazine was studied in vitro, using solvent extraction and thin layer chromatography followed by spectrophotometry for determination of the metabolites. Liver microsomes from rats, rabbits, pigs, guinea-pigs and cats and lung microsomes from rats, rabbits and pigs served as the enzyme sources. Kinetics of N-oxidation, N-demethylation, sulfoxidation and aromatic hydroxylation were measured with liver microsomes. Demethylation, sulfoxidation and aromatic hydroxylation underlie a substrate inhibition already at a perazine concentration of 1 mM, whereas N-oxidation usually is maximal with 2 mM perazine and starts to be inhibited at 4 mM perazine. In the concentration range tested (0·25-8 mM perazine) the N-oxide is always the major metabolite. Excessive N-oxidation has been observed in liver microsomes from individual pigs. Lung microsomes form substantial quantities of perazine N-oxide only, while other metabolites are produced to a negligible extent. An extremely high capacity for perazine N-oxidation was observed with rabbit lung microsomes, whereas microsomal preparations from rat and pig lungs N-oxidize perazine at a slower rate. © 1971.

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  • Ursula Breyer

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