Analgesic and immunomodulatory effects of codeine and codeine 6-glucuronide.
OBJECTIVE
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.
Srinivasan
V
V
Department of Pharmaceutics, University of Florida, Gainesville 32610, USA.
Wielbo
D
D
Simpkins
J
J
Karlix
J
J
Sloan
K
K
Tebbett
I
I
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D003061:Codeine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000276:Adjuvants, Immunologic; D000700:Analgesics; D009294:Narcotics; D009020:Morphine; C061773:codeine-6-glucuronide; D003061:Codeine