MICROSOMAL MIXED-FUNCTION AMINE OXIDASE - OXIDATION-PRODUCTS OF PIPERAZINE-SUBSTITUTED PHENOTHIAZINE DRUGS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 6  (3) , 232-239
Abstract
Oxidation products of fluphenazine, thioproperazine and trifluoperazine obtained in reactions catalyzed by homogeneous preparations of the hog liver microsomal mixed-function amine oxidase were isolated and identified. Approximately 0.5 g of metabolite of each piperazine-substituted phenothiazine drug was prepared in reactors containing, as catalyst, the purified oxidase covalently attached to glass beads. NMR spectra of the isolated products indicated that with all 3 substrates the enzyme preferentially catalyzes N-oxidation of the piperazine N furthest from the phenothiazine N atom. The enzyme-catalyzed oxidation is quite specific and oxidation of the S or N atoms in the phenothiazine ring could not be detected. Concentrations of piperazine- substituted phenothiazines required to half-saturate the amine oxidase were in the micromolar range and at pH 8.3 and 37.degree. C, all those tested were oxidized at approximately 2 .mu.mol/min per mg of enzyme. Kinetic constants for the piperazine-substituted phenothiazines were very similar to those obtained with phenothiazines containing a dimethylaminopropyl sidechain.

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