Summary
1. Acetylation of morphine at the 6-position changes its pharmacology. To see if similar changes are seen with codeine, we examined the analgesic actions of codeine and 6-acetylcodeine.
2. Like codeine, 6-acetylcodeine is an effective analgesic systemically, supraspinally and spinally, with a potency approximately a third that of codeine.
3. The sensitivity of 6-acetylcodeine analgesia to the mu-selective antagonists β-FNA and naloxonazine confirmed its classification as a mu opioid. However, it differed from the other mu analgesics in other paradigms.
4. Antisense mapping revealed the sensitivity of 6-acetylcodeine to probes targeting exons 1 and 2 of the mu opioid receptor gene (Oprm), a profile distinct from either codeine or morphine. Although heroin analgesia also is sensitive to antisense targeting exons 1 and 2, heroin analgesia also is sensitive to the antagonist 3-O-methylnaltrexone, while 6-acetylcodeine analgesia is not.
5. Thus, 6-acetylcodeine is an effective mu opioid analgesic with a distinct pharmacological profile.
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ACKNOWLEDGMENTS
This work was supported, in part, by grants from the National Institute on Drug Abuse to GWP (DA00220, DA07241) and to JP (DA09040) and a core grant from the National Cancer Institute (CA08748).
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Milo, S., Ansonoff, M., King, M. et al. Codeine and 6-Acetylcodeine Analgesia in Mice. Cell Mol Neurobiol 26, 1009–1017 (2006). https://doi.org/10.1007/s10571-006-9101-5
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DOI: https://doi.org/10.1007/s10571-006-9101-5