When it comes to tackling the opioid crisis, public health workers start with the drugs: fentanyl, morphine, heroin. But biochemists have a different focus: Not the opioids, but opioid receptors—the proteins the drugs latch onto within the body.
These receptors embed themselves in the walls of cells throughout the brain and peripheral nervous system. There, they serve as cellular gatekeepers, unlocking not just the painkilling properties for which opioids are prized, but the severe, addictive, and often lethal side effects that, in 2016, contributed to the deaths of more than 50,000 people in the US.
But it doesn't have to be that way. "The idea in the field for many years has been to make an opioid that provides beneficial analgesic properties without the harmful side effects," says pharmacologist Bryan Roth, a physician researcher at University of North Carolina School of Medicine. Design a drug that kills pain, not people.
To build that drug, though, researchers need to know the shape of its receptor. This week in the journal Cell, Roth and nearly two dozen of his colleagues report for the first time the structure of the kappa opioid receptor while it's bound to a drug molecule, a discovery that could accelerate the discovery of less-addictive—and less deadly—opioids.