Morphine‐6‐glucuronide: Actions and mechanisms

@article{Kilpatrick2005Morphine6glucuronideAA,
  title={Morphine‐6‐glucuronide: Actions and mechanisms},
  author={Gavin Kilpatrick and Terry W. Smith},
  journal={Medicinal Research Reviews},
  year={2005},
  volume={25}
}
Morphine‐6‐glucuronide (M6G) appears to show equivalent analgesia to morphine but to have a superior side‐effect profile in terms of reduced liability to induce nausea and vomiting and respiratory depression. The purpose of this review is to examine the evidence behind this statement and to identify the possible reasons that may contribute to the profile of M6G. The vast majority of available data supports the notion that both M6G and morphine mediate their effects by activating the µ‐opioid… 
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Morphine‐6‐glucuronide (M6G) for postoperative pain relief
TLDR
The present drug profile provides a review of the pharmacological properties of M6G, the clinical evidence relating to its efficacy and safety, and discusses its future role in the treatment of postoperative pain.
Sex-dependent influences of morphine and its metabolites on pain sensitivity in the rat
TLDR
It is demonstrated that intra-PAG M6G results in a greater analgesic response in females than morphine alone, which implicate sex differences in morphine metabolism, specifically M3G, as a contributing factor in the attenuated response to morphine observed in females.
Morphine-6-glucuronide: potency and safety compared with morphine
TLDR
M6G > 0.2 mg/kg is an effective analgesic with a slower onset but longer duration of action compared with morphine, and is an attractive alternative to morphine in the treatment of severe postoperative pain.
Morphine-6-Glucuronide: Morphine's Successor for Postoperative Pain Relief?
TLDR
Examination of morphine's active metabolite, morphine-6-glucuronide (M6G), suggests that M6G is possibly such a drug, which is well tolerated and produces adequate and long lasting postoperative analgesia.
Morphine glucuronidation increases its analgesic effect in guinea pigs.
TLDR
Modulation of morphine metabolism may result in variations in metabolite concentrations, leading to different analgesic responses to morphine, in an animal model that may be used to improve morphine effect in clinical practice.
A pharmacokinetic study of morphine‐6‐O‐sulfate in rat plasma and brain
TLDR
In vivo results indicate that M6S is not a prodrug of morphine, since M6s is not biotransformed into MOR in plasma after either i.p. or oral administration, and MOR was not detected in brain.
Evaluation of morphine‐like effects of the mixed mu/delta agonist morphine‐6‐O‐sulfate in rats: Drug discrimination and physical dependence
TLDR
The mixed μ/δ agonist activity of M6S failed to completely protect against the development of physical dependence, but delayed tolerance development to behavioral effects and resulted in decreased morphine‐like subjective effects, perhaps implying a decreased abuse liability over μ agonists.
A novel finding of nalbuphine-6-glucuronide, an active opiate metabolite, possessing potent antinociceptive effects: Synthesis and biological evaluation.
TLDR
In conclusion, intracisternal administration of N6G exhibited a stronger analgesic response than nalbuphine in the pain tests after both cold and mechanical stimuli, but N3G had no obvious effect.
A review of morphine and morphine-6-glucuronide's pharmacokinetic-pharmacodynamic relationships in experimental and clinical pain.
TLDR
A detailed overview of the published human population pharmacokinetic-pharmacodynamic studies for morphine analgesia in addition to basic drug disposition and pharmacological properties of morphine and its analgesic active metabolite, morphine-6-glucuronide, that may help identify future covariates are provided.
Conditioned place preference induced by morphine and morphine-6-glucuronide in mice
TLDR
Morphine-6-glucuronide and M6G demonstrated comparable reward effects, at doses that differed depending on which compartment the mice were conditioned in, and M3G showed a tendency to exhibit aversive properties.
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TLDR
It is speculated that M6G may exhibit analgesic effects while causing fewer adverse effects than morphine, and may be contemplated as an analgesic for short term postoperative analgesia, especially for intrathecal analgesic therapy.
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TLDR
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TLDR
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