Studies on the hepatotoxicity of some centrally acting drugs

ABSTRACT

Exposure of mice to halothane [1.5% in 0[2]] or their treatment with single doses of chlorpromazine [CPZ, 10 mg/kg] or reserpine [2.5 mg/kg] caused depletion of glutathione [GSH] and accumulation of lipid peroxidotion products [assessed as malonaldehyde] in the liver and an increase in the activity of aspartate aminotransferase [AST] and alanine aminotransferase [ALT] in the serum. These changes could be abolished or inhibited by pretreatment with alpha adrenergic blockers [phentolamine and yohimbine]. The beta blocker propranolol was not effective. Depletion of catecholamines by reserpine abolished the effect of a dose of chlorpromazine administered 24 hours later. In a multiple-dose experiment with chlorpromazine [10 mg/kg/dayX7], reserpine [2.5 mg/kg/dayX7] or maprotiline [5mg/kg/dayX7], the changes in the biochemical parameters, indicative of hepatotoxic reaction, were seen with chlorpromazine only. It appears that the hepatotoxicity of halothane and chlorpromazine may be mediated through the adrenergic system and antagonized by blocking alpha-adrenergic receptors or depleting catecholamine stores