Although activation of the μ-opioid receptor (MOR) provides potent analgesia and remains central to pain management, its agonists are associated with adverse effects such as respiratory depression, tolerance, dependence and pruritus. Bifunctional μ-/κ-opioid receptor (MOR/KOR) agonists aim to retain MOR-driven analgesia while leveraging the antipruritic and complementary analgesic effects of KOR activation to improve overall therapeutic tolerability.