Effect of alkali metals on chlorpromazine toxicity in the mouse

Abstract

The effect of short-term injection of chlorpromazine alone or combined with either LiCl or CsCl (1 mEq/kg/day) on 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. The results indicate the enhancement of chlorpromazine toxicity by prolonged treatment with LiCl and suggest their contraindication.