morphine3glucuronide

Morphine-3-glucuronide (M3G) is a major metabolite of morphine formed by the body’s glucuronidation processes. It is produced primarily in the liver by UDP-glucuronosyltransferase enzymes, notably UGT2B7, through conjugation of morphine with glucuronic acid at the 3-hydroxyl group. A second morphine glucuronide, morphine-6-glucuronide (M6G), is formed at a different site. After formation, M3G is largely excreted in the urine as a glucuronide conjugate, reflecting hepatic metabolism and renal clearance.

Pharmacologically, M3G is not considered analgesic. It has little or no affinity for μ-opioid receptors and does not contribute to pain relief in the same way as morphine or M6G. Some studies suggest that, at higher concentrations, M3G may have neuroexcitatory effects and could be associated with certain adverse central nervous system symptoms in animal models. In humans, accumulation of M3G—especially in individuals with reduced renal function—has been reported in rare cases, though a direct causal link to specific symptoms remains inconclusive.

Clinical significance revolves largely around renal function and morphine dosing. Because M3G is excreted in urine, impaired kidney function can lead to higher circulating levels of this metabolite, contributing to overall drug exposure and potentially to adverse effects. Clinicians may monitor renal status and adjust morphine therapy accordingly to balance analgesia with the risk of metabolite accumulation.

See also morphine-6-glucuronide.