Chlorpromazine and lithium interaction: a biochemical and histological study

Biochemical and histological studies on the effect of separate and combined administration of LiCl and of chlorpromazine (CPZ) on female C57BL/6J mice were performed. Mice were divided into 4 groups. One group was given an intraperitoneal injection daily of CPZ HCl, 5 mg/kg for 4 days followed by 4 more days of a daily dosage of 10 mg/kg. A second group was maintained on 0.4% (w/v) LiCl solution as the sole drinking fluid for 8 consecutive days and a third group received the same LiCl solution but with daily CPZ injection as the initial group for 8 days. The fourth group served as saline-controls. Hepatic liver alcohol dehydrogenase was induced by combined drug treatment from respective controls. The Li-treatment inhibited mitochondrial liver aldehyde dehydrogenase, and coadministration of CPZ with LiCl antagonized this effect. Mice treated with CPZ showed corneal cellularity and mitotic figure appearance without inflammation. The LiCl treated mice displayed variations in base corneal cell size, shape and pigmentation with aggregation of the nuclei, and the presence of mitotic activity inflammation. Mice receiving combined drug treatment showed similar corneal alterations, but mitotic figures were found above base cell layer suggesting an enhanced corneal toxicity. The results suggest a drug-drug interaction phenomenon which may explain some of their adverse reaction when given concurrently.