On the specificity of naloxone as an opiate antagonist

doi:10.1016/0024-3205(79)90403-X

Life Sciences

Volume 25, Issue 19, 5 November 1979, Pages 1621-1631

https://doi.org/10.1016/0024-3205(79)90403-X Get rights and content

Abstract

Since the discovery of endogenous opioid peptides in brain (68,69,97,113, 128) and the pituitary gland (26,81,105,125) there has been considerable interest in their possible roles in a variety of physiological and pharmacological processes. Many studies have used antagonism by naloxone as a criterion for implicating endogenous opiates in a process, assuming that naloxene has no pharmacological actions other than those related to blockade of opiate receptors. The doses of naloxene used are often higher than those required to antagonize the analgesic and other effects of morphine. However, multiple forms of opiate receptors are present in nervous tissue and higher concentrations of naloxene are required to antagonize effects mediated by some of these receptors (83). Although the earlier literature supports the assumption that the effects of naloxene are due to the blockade of opiate receptors (87), there are an increasing number of reports which indicate that naloxene may have pharmacological actions unrelated to opiate receptor blockade. The subsequent review serves to emphasize that antagonism by naloxene is a necessary but not sufficient criterion for invoking the mediation of a response by an endogenous opiate (61). Additional lines of evidence which serve to strengthen the conclusion that endogenous opiates mediate a process will be considered.

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Further studies in rats by Spanagel et al. (1991) have demonstrated that the β-endorphin effects are dose dependent: a small amount (2.5-5 μgr) stimulates locomotor activity via dopamine release by the nucleus accumbens, whereas a higher amount (7 μgr) elicits catalepsy but not dopamine release. The main criteria required to assess the involvement of an opioid mechanism are: (a) morphine potentiation and naloxone antagonization (Sawynock et al., 1979) and (b) abolition in morphine tolerant animals (Akil et al., 1984). Before discussing opioid mechanisms, it is important to underline that morphine has a different analgesic effect on tonic and phasic experimental pain in animals and in acute and chronic pain in humans.
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In our model, NLX alone significantly decreased TI and increased f in comparison to the solvent. In the literature, various stimulant effects have been attributed to NLX (Isom and Elshowihy, 1982; Sawynok et al., 1979). Additionally, NLX has been shown to enhance ventilatory response (increase in f and VT) to hypercapnia (Schlenker et al., 1997) or hypoxia (Olson, 1987).
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^☆: Studies of the authors were supported by the Medical Research Council of Canada, Non-Medical Use of Drugs Directorate, Health and Welfare Canada, the Sellers Foundation and the Richardson Foundation.

²: Postdoctoral Fellow of the Medical Research Council.

³: Career Investigator of the Medical Research Council.

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MinireviewOn the specificity of naloxone as an opiate antagonist☆

Abstract

J. Pediatr.

Neurosci. Lett.

Life Sci.

Life Sci.

Biochem. Pharmacol.

Life Sci.

Neuropharmacology

Europ. J. Pharmacol.

Life Sci.

Life Sci.

Nueropharmacology

Neurosci. Lett.

Life Sci.

Prog. Neuro-Psychopharmacol.

Europ. J. Pharmacol.

Life Sci.

Brain Res.

Life Sci.

Life Sci.

Biochem. Biophys. Res. Comm.

J. Am. Coll. Emer. Phys.

Life Sci.

Life Sci.

Biochem. Biophys. Res. Comm.

Science

Nature

Biochem. Soc. Trans.

Anaesthiol.

J. Pharmacol. Exp. Ther.

Science

Brain Res. Bull.

Naunyn-Schmiedeberg's Arch. Pharmacol.

Pharmacologist

Nature

Life Sci.

Arch. Int. Pharmacodyn. Ther.

Science

Life Sci.

J. Pharmacol. Exp. Ther.

J. Pharmacol. Exp. Ther.

Anaes. Analg.

Life Sci.

Psychopharmacology

Minireview
On the specificity of naloxone as an opiate antagonist☆