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Another multitarget MOR-DOR agonist, SRI-22141, was tested in the clinically relevant models of HIV neuropathy and chemotherapy-induced peripheral neuropathy, in which it was found that while providing equal or enhanced efficacy versus morphine, the tolerance was significantly reduced, with almost non-dependence during the course of repeated administration [59]

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New or worsening nephropathy, defined as persistent macroalbuminuria, persistent doubling of the serum creatinine level, and a creatinine clearance of 30 ml/min/1.73 m 2 should receive metformin and SGLT2i (Fig