Safer opioids in mice with a sideways approach

Opioids are some of the oldest known treatments for pain relief, but they can cause serious side effects. A team of researchers including Susruta Majumdar, a medicinal chemist and pharmacologist at Washington University in St. Louis, has designed an opioid that latches on to receptors in the brain by homing in on water molecules at a key position ( ACS Cent. Sci. 2024, DOI: 10.1021/acscentsci.4c00525 ). The small molecule relieved pain in mice while also appearing to have fewer dangerous side effects than morphine. Opioids relieve pain upon binding to opioid receptors in the brain. Scientists have previously found that opioids with lower efficacy than drugs like fentanyl and morphine are still powerful enough to relieve pain, and are potentially safer. Buprenorphine, which is used to treat people with opioid use disorder, is one example. Majumdar’s group wanted to make an opioid with lower efficacy than fentanyl. The team had