Separation of opioid analgesia from respiratory depression: Evidence for different receptor mechanisms

Geoffrey Ling, K. Spiegel, S. H. Lockhart, G. W. Pasternak

Research output: Contribution to journalArticle

Abstract

Pretreating rats 24 h earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P < .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effect of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume232
Issue number1
StatePublished - Jan 1 1985
Externally publishedYes

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Respiratory Insufficiency
Analgesia
Morphine
Opioid Analgesics
Analgesics
metkephamid
Opioid Peptides
Tail
Gases
naloxonazine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Separation of opioid analgesia from respiratory depression : Evidence for different receptor mechanisms. / Ling, Geoffrey; Spiegel, K.; Lockhart, S. H.; Pasternak, G. W.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 232, No. 1, 01.01.1985, p. 149-155.

Research output: Contribution to journalArticle

Ling, Geoffrey ; Spiegel, K. ; Lockhart, S. H. ; Pasternak, G. W. / Separation of opioid analgesia from respiratory depression : Evidence for different receptor mechanisms. In: Journal of Pharmacology and Experimental Therapeutics. 1985 ; Vol. 232, No. 1. pp. 149-155.
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