Kappa3 receptors and levorphanol-induced analgesia

L. Tive, K. Ginsberg, C. G. Pick, G. W. Pasternak

Research output: Contribution to journalArticlepeer-review

Abstract

Levorphanol is a widely used opiate analgesic. Although structurally related to morphine, levorphanol has high affinity for a number of receptor subtypes, including both kappa1, and kappa3. Prior reports had implicated a kappa component of levorphanol-induced antinociception. Evidence is now presented suggesting that levorphanol-induced analgesia is produced by a mixture of mu and kappa3 mechanisms. Levorphanol was a potent analgesic in the tail-flick assay, when given systemically, spinally or supraspinally. Isobolographic analysis of the combined administration of levorphanol, spinally and supraspinally implied synergistic interactions. Naloxonazine reduced levorphanol-induced analgesia, implicating a role for mu1 receptors. The kappa1 antagonist nor-binaltorphimine at a dose which reversed analgesia induced by U50,488H did not antagonize levorphanol-induced analgesia. Additional studies revealed no cross tolerance in either direction, between levorphanol with the kappa1 analgesic U50,488H. Together, these results strongly argue against a role for kappa1, receptors in levorphanol-induced analgesia. However, mice tolerant to the kappa3 analgesic, naloxone benzoylhydrazone (NalBzoH), showed cross tolerance to levorphanol, implying a role of kappa3 mechanisms in levorphanol-induced analgesia.

Original languageEnglish
Pages (from-to)851-856
Number of pages6
JournalNeuropharmacology
Volume31
Issue number9
DOIs
StatePublished - Sep 1992
Externally publishedYes

Keywords

  • analgesia
  • kappa receptors
  • morphine
  • pain

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