Unidirectional analgesic cross-tolerance between morphine and levorphanol in the rat

Dwight E. Moulin, Geoffrey S.F. Ling, Gavril W. Pasternak

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Clinically, patients often demonstrate incomplete cross-tolerance between opiate analgesics. Although dispositional and pharmacokinetic factors may be a factor, our results suggest that differences in selectivity of various opioids for those opioid receptor subtypes involved in analgesia, mu1, kappa and delta, also play an important role. In binding studies, levorphanol potently labelled all 3 classes whereas morphine was relatively selective for mu sites. Levorphanol infusions yielded tolerance to both morphine and levorphanol while morphine infusions selectively produced tolerance to morphine. This unidirectional tolerance might be due to the selectivity of morphine for mu receptors compared to levorphanol's ability to interact more potently with other relevant receptor subtypes. These observations raise the possibility that the order in which different opioid analgesics are administered may be of clinical significance.

Original languageEnglish (US)
Pages (from-to)233-239
Number of pages7
Issue number2
StatePublished - May 1988


  • Analgesia
  • Morphine
  • Opiate receptor

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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