Possible DA Agonist Properties of Naloxone

Abstract

Naloxone is widely if not universally considered to be a pharmacologically ‘pure’ opiate (μ) receptor antagonist virtually devoid of agonist action when administered in moderate dosages. However, naloxone (NX) appears to possess a striking number of DA agonist properties. Thus, some investigators have found NX capable of inducing stereotyped rearing and locomotor activity in habituated rats (a controversial finding), and decrease serum prolactin levels, improve Parkinsonism, enhance copulatory performance in sexually sluggish animals, and increase striatal HVA levels, in mimicry of centrally acting DA agonists. NX can also significantly potentiate the central effects induced by DA agonists including DA agonist (d-amphetamine) induced ³H-dopamine release, and antagonize a number of the central effects elicited by DA release inhibiting agents. Finally, virtually all of the central effects of morphine reversible by NX have also been found to be antagonized by a variety of dopamine agonists; while DA release inhibiting agents can abolish the ability of NX to antagonize morphine induced effects. Thus, NX may be exerting its central effects through a dopaminergic mechanism. Since NX does not bind DA receptors, it is quite likely that NX may ultimately antagonize the central effects of morphine by enhancing DA release from DA terminals upon which opiate receptors are localized. The same opiate receptors, shown to be localized on DA nerve terminals, have already been implicated in opiate mediated modulation of DA release.