The phdodegradation of chlorpromde, a drug frequently uaed in pmychotherapy, was examined under diiterent eets of experimental conditions. A primary culture of rat hepatocytes was used to evaluate the poedble hepatotoxicity of the chlorpromozine photoproducts, kemping in mind the following c r i t e r h leakage of cytomlic enzymes; attachment index to culture plates, and albumin synthesis. Cells exposed to conoentrations greater than lo4 Mof the photomixtures showed extensive leakage of GOT and GPT into the culture medium and, at the same time, the cell attachment was seriously
impaired. A concentration of lo-' M of the photoprod-
Ucte proved capable of inhibiting the synthesis of albumin (80%). Photoproducts obtained after aerobic irradiations were as toxic for hepatocytes as thoee found in anaerobic conditions. The implications of our results in connection with the relevance of oxygen-dependent photoreactiom of chlorpromazine to its phototoxicity, and the padble appearance of hepatic alterations in patients treated with the drag after expoeure to the sunlight, are discuseed.
Chlorpromazine (CPZ) is a drug frequently prescribed in psychotherapy, but its use in prolonged and high dosage treatment is known to cause adverse light-induced biological processes, such as allergic skin reactions, ocular changes and mutagenic effects (1, 2). Previous investigations have dealt with the photolytic degradation of CPZ, in an attempt to establish some correlations between the photochemical reactivity "in uitro" and the chemical processes which are responsible at the molecular level for the observed "in uiuo" photosensitivity (3-9). In this respect, it is known that preirradiated solutions of CPZ c a w red blood cell lysis, are toxic to macrophages, inactivate lysosomal enzymes and produce marked cutaneous irritations when injected into guinea pig skin (10-14).
It is especially worth noting that the phototoxic effects of a drug may not necessarily be restricted to the skin. Working with chlordiazepoxide as a model, Bakri et al.