A dual-targeting painkiller

Abstract

Pain Opioids are among the most effective treatments for severe pain. Their pain-relieving effects are mediated by activation of the mu opioid receptor (MOR). Unfortunately, selective MOR agonists induce diverse side effects, including respiratory depression, tolerance, hyperalgesia, and dependence. Recently, activation of the nociceptin/orphanin FQ peptide receptor (NOR) has been reported to enhance MOR agonist–induced analgesia without producing side effects. Ding et al. developed a bifunctional MOR/NOR agonist called AT-121, which showed potent analgesic effects in nonhuman primates without inducing hyperalgesia, respiratory depression, or dependence. Bifunctional MOR/NOR agonists might thus represent a safe and effective pharmacological tool for treating severe pain. Sci. Transl. Med. 10 , eaar3483 (2018).