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Oxidation of Amino Acids by Chlorpromazine Cation Radical and Co-Catalysis by Chlorpromazine

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DOI: 10.4236/pp.2012.31005    4,629 Downloads   8,631 Views   Citations

ABSTRACT

The long-tem use of chlorpromazine (CPZ) may cause severe side effects. This property of CPZ might be related to pro-oxidant effects of the chlorpromazine cation radical (CPZ·+), which can be easily generated by catalytic action of peroxidases, including the neutrophil myeloperoxidase (MPO) and by methemoglobin. Aiming the comprehension of a putative physiological effect of CPZ·+ upon biomolecules, in this work we studied the reactivity of CPZ·+ with amino acids and the co-catalytic effect of CPZ during the oxidation of amino acids by horseradish peroxidase (HRP)/H2O2 system. We also studied whether natural blood plasma components as ascorbic acid, uric acid and nitrite could inhibit the oxidative effect of CPZ·+. We found that tryptophan, tyrosine and cysteine were easily oxidized by pure CPZ·+. Other amino acids as methionine, glycine, phenylalanine, aspartic acid and lysine were unreactive. The decomposition of CPZ·+ was exacerbated by uric acid, ascorbic acid and nitrite, provoking inhibition in the amino acids oxidation. In experiments with HRP/H2O2, and using CPZ as a co-catalyst, a strong effect upon oxidation of tryptophan, tyrosine and cysteine was obtained. It was also found that tryptophan was more reactive than tyrosine with CPZ·+, a feature that could be related to the recently described favorable interaction between tryptophan and CPZ. The use of CPZ as a co-catalyst is discussed regarding its role in the efficient oxidation of tryptophan.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

V. Ximenes, G. Quaggio, F. Graciani and M. Menezes, "Oxidation of Amino Acids by Chlorpromazine Cation Radical and Co-Catalysis by Chlorpromazine," Pharmacology & Pharmacy, Vol. 3 No. 1, 2012, pp. 29-36. doi: 10.4236/pp.2012.31005.

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