When people die from overdoses of opioids, whether prescription pain medications or street drugs, it is the suppression of breathing that almost always kills them. The drugs act on neuronal receptors to dull pain, but those in the brain stem also control breathing. When activated, they can signal respiration to slow, and then stop. The results are well-known: an epidemic of deaths—about 64,000 people in the United States alone last year.
Countering this lethal side effect without losing opioids' potent pain relief is a challenge that has enticed drug developers for years. Now, for the first time, the U.S. Food and Drug Administration (FDA) in Silver Spring, Maryland, is considering whether to approve an opioid that is as effective as morphine at relieving pain and poses less risk of depressing breathing.
Trevena, a firm based in Chesterbrook, Pennsylvania, announced on 2 November that it has submitted oliceridine, an intravenous opioid meant for use in hospitalized patients, to FDA for marketing approval. The drug, which would be marketed under the name Olinvo, is the most advanced of what scientists predict will be a growing crop of pain-relieving "biased agonists"—so called because, in binding a key opioid receptor in the central nervous system, they nudge it into a conformation that promotes a signaling cascade that kills pain over one that suppresses breathing. And in a paper out this week in Cell, a veteran opioid researcher and her colleagues unveil new biased opioid agonists that could surpass oliceridine, though they haven't been tested in people yet.