Novel Opioid Receptor Agonists with Reduced Morphine-like Side Effects

Opioid analgesics, such as morphine, are widely employed in the treatment of moderate to severe pain. However, they are notorious for abuse liability and respiratory depression. Therefore circumventing the side effects, such as euphoria, addiction, respiratory depression and gastrointestinal adverse reactions, is of extensive importance. Recently, a large number of research results have revealed that such morphine-like side effects are not inevitable, and they focus on the novel approaches to disconnecting the analgesics from adverse effects. In this review, we mainly discuss the approaches including biasing the GPCRs over beta-arrestin2 recruitment (TRV130, PZM21, HS665), the positive allosteric modulators of the MOR (BMS-986122) and multiple agonists of opioid receptors subtypes (SNC80, DPI-125). Besides these, we also introduce the key protein sites of MOR and beta-arrestin2 recruitment briefly.