morphine6glucuronide

Morphine-6-glucuronide, abbreviated as M6G, is a glucuronide metabolite of morphine formed in the liver by UDP-glucuronosyltransferases, principally UGT2B7. It is an active opioid analgesic that binds the mu-opioid receptor and can contribute substantially to morphine’s overall analgesic effect.

Formation and metabolism: After morphine administration, the drug is conjugated with glucuronic acid to yield M6G and morphine-3-glucuronide (M3G). M6G is more polar than morphine, which limits its penetration across the blood-brain barrier compared with parent morphine, but it still provides analgesia.

Pharmacology: As a mu-opioid receptor agonist, M6G produces analgesia and shares the adverse effects typical of opioids, such as sedation, respiratory depression, and constipation. Some studies and clinical observations suggest M6G can be more potent per milligram than morphine and may have a longer duration of action in humans, though estimates of potency vary.

Pharmacokinetics: M6G is primarily eliminated by the kidneys. It is excreted in urine both as unchanged drug and as glucuronide conjugate. Renal function strongly influences clearance and half-life; in renal impairment, M6G can accumulate, leading to prolonged analgesia and an increased risk of respiratory depression.

Clinical considerations: In patients with reduced renal function, morphine dosing requires caution due to M6G accumulation. Clinicians may adjust doses, monitor for sedation and respiratory status, or choose alternative opioids with less problematic active metabolites.

Relationship to M3G: Morphine-3-glucuronide does not contribute to analgesia and may be neuroexcitatory in some contexts, whereas M6G remains the principal active metabolite contributing to analgesia.