Effect of alkali metals on chlorpromazine toxicity in the mouse

The effect of short-term injection of chlorpromazine alone or combined with either LiCl or CsCl (1 mEq/kg/day) in organ toxicity was studied in the albino male mouse. Chlorpromazine was administered by gradual dose build-up regimens from 5 mg/kg to 50 mg/kg which was attained over a 40-day period followed by abrupt drug withdrawal for a subsequent 25-day observation period. Histological evaluation of 10 tissues selected indicates that the liver was the target organ. The Li-treatment resulted in variable liver lobular size with loss of cell definition and the kidney showed focal lymphatic aggregates related to vascular channel. Chlorpromazine-treated mice displayed variation in liver nuclei size and in cell structure definition. Combined injection of LiCl with the phenothiazine drug resulted in alteration in size of liver nuclei with a slight midlobular distribution. Minimal changes in lobular liver cells were noted subsequent to the Cs-treatment. This is compared to some dilation of liver central veins and few variations in hepatocyte size after combined injection of CsCl with chlorpromazine. There was a reduction in body weight of animals treated with the LiCl and chlorpromazine combination compared to that of mice receiving the chlorpromazine alone or in combination with CsCl. A rebound in body weight loss occurred during drug withdrawal in mice pretreated with chlorpromazine alone or combined with CsCl but not in mice coadministered LiCl with chlorpromazine. Mortality score indicates a profound lethal effect during administration of LiCl with the high dosage of the chlorpromazine used which was persistent during drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)