Antioxidant action and photosensitizing effects of three different chlorpromazines

Chlorpromazine inhibits by about 60% the lipid peroxidation stimulated by Fe2+/ascorbate in liposomes and the lipid peroxidation stimulated by cumene hydroperoxide in microsomes. Under the same conditions, two new synthetic derivatives of chlorpromazine, i.e., a N-benzoyloxymethylchlorpromazine and a N-pivaloyloxymethylchlorpromazine, induce no more than a 20% inhibition. On the other hand, when the different chlorpromazines are entrapped in liposomes and subsequently irradiated with near-UV light, they act as photosensitizing agents giving rise to lipid peroxidation. The latter is quite extensive in the presence of chlorpromazine or N-pivaloyloxymethylchlorpromazine, whereas it is drastically lower in the presence of N-benzoyloxymethylchlopromazine. The N-benzoyloxymethylchlorpromazine molecule, despite its low photodynamic effect, retains its neuroleptic properties. The possible mechanisms of the antioxidant and prooxidant actions of these compounds are discussed.