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Related Experiment Videos

Morphine-6-glucuronide, a potent mu agonist.

G W Pasternak1, R J Bodnar, J A Clark

  • 1Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY.

Life Sciences
|December 28, 1987
PubMed
Summary
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Morphine glucuronides were studied for their effects on opioid receptors. Morphine-6-glucuronide is a potent mu-opioid receptor agonist with analgesic and seizure-inducing properties, unlike morphine-3-glucuronide.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Medicinal Chemistry

Background:

  • Morphine is a potent opioid analgesic, but its metabolites' pharmacological activities are not fully understood.
  • Morphine undergoes glucuronidation to form morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G).
  • Previous research suggests M6G may possess analgesic properties, while M3G is associated with neuroexcitatory effects.

Purpose of the Study:

  • To investigate the receptor binding affinities and in vivo pharmacological effects of morphine-3-glucuronide and morphine-6-glucuronide.
  • To compare the potency and efficacy of M3G and M6G with morphine in preclinical models.

Main Methods:

  • Radioligand binding assays were performed to determine the affinity of M3G and M6G for mu, delta, and kappa opioid receptors.

Related Experiment Videos

  • In vivo studies involved microinjections of M3G and M6G into the periaqueductal gray (PAG) of rodents.
  • Behavioral effects, including analgesia and seizure activity, were assessed following administration.
  • The role of naloxone, an opioid antagonist, was evaluated in blocking the observed effects.

    • Main Results:

    • Morphine-6-glucuronide demonstrated high affinity for mu-opioid receptors, comparable to morphine, but did not bind to delta or kappa receptors.
    • Morphine-3-glucuronide exhibited poor affinity for all tested opioid receptors.
    • Microinjections of M6G into the PAG were significantly more potent (up to 20-fold) than morphine in producing analgesia.
    • High doses of M6G induced profound seizure activity, which was reversible by naloxone.
    • Microinjections of M3G into the PAG were without significant effect.

    Conclusions:

    • Morphine-6-glucuronide is a potent mu-opioid receptor agonist with significant analgesic and proconvulsant properties.
    • The pharmacological actions of M6G are mediated through the mu-opioid receptor and are sensitive to naloxone.
    • Morphine-3-glucuronide does not appear to contribute significantly to the central effects of morphine via mu-opioid receptor agonism.