Analgesic and immunomodulatory effects of codeine and codeine 6-glucuronide

Pharm Res. 1996 Feb;13(2):296-300. doi: 10.1023/a:1016059618633.


Purpose: The antinociceptive and immunosuppressive effects of codeine and codeine 6-glucuronide were determined in rats after intracerebroventricular administration.

Methods: Codeine 6-glucuronide was synthesized using a modification of the Koenigs-Knorr reaction. A lipophilic intermediate formed during synthesis, methyl [codein-6-yl-2,3,4-tri-O-acetyl-beta-D-glucopyranosid] uronate, was also tested. Morphine was used as a positive control to compare antinociceptive potencies of these compounds.

Results: All compounds tested produced significant analgesic responses, as assessed by the tail flick model. Additionally, codeine 6-glucuronide showed significantly less immunosuppressive effects than codeine in vitro.

Conclusions: We conclude that codeine 6-glucuronide and related compounds may have clinical benefit in the treatment of pain in immune compromised patients.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Analgesics / pharmacology
  • Animals
  • Codeine / analogs & derivatives*
  • Codeine / pharmacology*
  • Injections, Intraventricular
  • Male
  • Morphine / pharmacology
  • Narcotics / pharmacology*
  • Rats
  • Rats, Sprague-Dawley


  • Adjuvants, Immunologic
  • Analgesics
  • Narcotics
  • Morphine
  • codeine-6-glucuronide
  • Codeine