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)/H 2 O 2 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/H 2 O 2 , 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.
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