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. 1992 Jan;65(1):122–126. doi: 10.1038/bjc.1992.23

Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide.

D Hucks 1, P I Thompson 1, L McLoughlin 1, S P Joel 1, N Patel 1, A Grossman 1, L H Rees 1, M L Slevin 1
PMCID: PMC1977344  PMID: 1310249

Abstract

The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu 1 or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained.

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Selected References

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