Effects of chloroquine pretreatment on lethal dose of morphine and on morphine metabolism in rats

Abstract

The previous administration of chloroquine to normal rats resulted in a significant increase in the lethal dose of morphine and in a higher amount of conjugated morphine in the liver. No differences were found on normorphine formation in liver of treated and untreated groups. The blood levels of free morphine at death were not significantly different in pretreated and control rats. Pretreatment with chloroquine did not prevent the onset of the depressant respiratory effects of morphine. Chloroquine pretreatment induced a marked increase of the in vitro conjugation of morphine, suggesting that chloroquine acts as a morphine antagonist through a metabolic mechanism. The implication of these effects on morphine tolerance are discussed. © 1969.