Does naloxone always act as an opiate antagonist?

Abstract

Evidence for the ability of the opiate antagonist naloxone to block a variety of metabolic effects exerted by morphine and non-opiate drugs is reviewed. Naloxone prevents or reverses the following effects in the rat: (a) the chronic morphine-induced increase in liver [NADPH]; (b) the consequent chronic morphine-induced inhibition of liver tryptophan pyrrolase activity; (c) the resultant chronic morphine-induced enhancement of brain 5-hydroxytryptamine synthesis; (d) the similar effects on liver and brain tryptophan metabolism exerted chronically by other drugs of dependence (ethanol, nicotine and phenobarbitone); (e) the acute ethanol-induced increase in the hepatic [NADH]/[NAD] ratio. Naloxone also (f) inhibits basal and stimulated lipolysis in fed and 24hr-starved rats. This leads to prevention of (g) the consequent increase in the availability of circulating free tryptophan, and (h) the resultant tryptophan-mediated decrease in liver 5-aminolaevulinate synthase activity. The question of how many of these effects involve changes in endogenous opiates or at opiate receptors is not clearly understood at present and thus merits investigation. However, because most of the above effects are explained on biochemical grounds, and in view of evidence from behavioural and pharmacological studies [see (1)], the possibility must be considered that many of the actions of naloxone may be unrelated to its opiate-receptor-antagonistic properties.