title: Comparison of the antinociceptive effect of morphine, methadone, buprenorphine and codeine in two substrains of Sprague-Dawley rats.
abstract: Sprague-Dawley rats from two different vendors, Möllegård, Denmark and B&K Universal, Sweden, have been tested for the antinociceptive effect of morphine, methadone, buprenorphine and codeine on the hot plate. Morphine and methadone had significantly weaker effect in Möllegård rats compare to B&K rats. In contrast, the effect of buprenorphine was stronger in Möllegård rats than in B&K rats and the effect of codeine was similar in the two substrains. Plasma levels of morphine, morphine-6-glucuronide, morphine-3-glucuronide, buprenorphine and norbuprenorphine were determined at two time points after drug injection. Möllegård rats had significantly lower mean plasma level of morphine and significantly higher ratio of morphine-3-glucuronide/morphine at 30 min, compared to B&K rats. No difference was seen for the metabolism of buprenorphine in the two substrains. The results suggest that Möllegård rats metabolize morphine to morphine-3-glucuronide to a greater extent than B&K rats, and this may at least partly underlie the substrain difference in the effect of morphine. It is also suggested that the antinociceptive mechanisms of buprenorphne may be different from those of morphine and methadone.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Neurophysiology, Karolinska Institute, Huddinge University Hospital, S-141 86, Stockholm, Sweden.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bulka
authors.forename: Poli Francois
authors.initials: PF
authors.lastname: Kouya
authors.forename: Ylva
authors.initials: Y
authors.lastname: Böttiger
authors.forename: Jan-Olof
authors.initials: JO
authors.lastname: Svensson
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Xu
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Wiesenfeld-Hallin
mesh_terms: D000700:Analgesics / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D003061:Codeine / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000097:blood; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
chemical_list: D000700:Analgesics; D009022:Morphine Derivatives; D002047:Buprenorphine; D009020:Morphine; C043585:norbuprenorphine; C018108:morphine-3-glucuronide; D008691:Methadone; D003061:Codeine