Phenothiazine phototoxicity: toxic chlorpromazine photoproducts

The effect of preirradiated chlorpromazine (CPZ) solutions has been studied in vivo in the guinea pig and in vitro in a yeast culture. With intracutaneous administration of CPZ solutions preirradiated with long-wave ultraviolet radiation (UVA), an inflammatory response was attained equaling the response achieved when nonirradiated solutions were injected and the skin of the animals was subsequently irradiated with UVA. Preirradiated CPZ was not toxic to the yeast culture. During irradiation the pH of the CPZ solution changed, indicating an accumulation of acid photoproducts. Nonphototoxic phenothiazines and related tricyclic drugs failed to change their pH following irradiation whereas phototoxic compounds behaved like CPZ. The low pH alone could not account for the inflammatory response in vivo, as neutralized irradiated CPZ solutions still induced inflammation, and acidified, nonirradiated solutions failed to cause a reaction. CPZ phototoxicity seems mainly to be due to the effect of photoproducts. The nature of these is not known, but it is suggested that the stable free radical of CPZ might be an active principle.