Nearly all of the roughly 64,000 Americans who died from opioid overdoses in 2016 succumbed because their breathing shut down, triggered by the effects of the drugs on important receptors in the brain stem. When they are activated, μ-opioid receptors potently relieve pain. They also control respiration. Now, for the first time, a drug that in binding these receptors causes powerful pain relief with less respiratory suppression is being evaluated for marketing approval by the Food and Drug Administration. Biotech company Trevana’s drug, oliceridine, acts as a μ-opioid receptor to activate a pain-relieving signaling pathway with less triggering of a separate path that leads to depressed breathing. Oliceridine is the first so-called “biased opioid” to emerge from human clinical trials. There will certainly be more: In a paper published in Cell this week, scientists at the Scripps Research Institute in Jupiter, Florida, have rigorously demonstrated for the first time in mice that the more biased a compound is toward activating the pain-relieving pathway, the less it suppresses breathing.
‘Biased’ opioids could yield safer pain relief