| Abstract: |
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 beta-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. |
| Keywords: |
genetics; dose response; comparative study; methodology; mouse; animal; mouse mutant; animals; mice; mice, knockout; dose-response relationship, drug; structure activity relation; structure-activity relationship; mice, inbred c57bl; physiology; c57bl mouse; mice, inbred strains; narcotic analgesic agent; evaluation; drug derivative; mouse strain; morphine; analgesics, opioid; analgesia; mu opiate receptor; receptors, opioid, mu; oprm protein, mouse; codeine; acetylcodeine
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