Fentanyl, a powerful opioid pain reliever, is the leading cause of overdose deaths in the United States. With the aim of improving the drug’s safety profile to make it less lethal and addictive without eliminating its ability to alleviate pain, a team of researchers, led by scientists at the Center for Clinical Pharmacology at Washington University School of Medicine in St. Louis and the University of Health Sciences & Pharmacy in St. Louis, have altered the drug’s chemical properties and the way that it binds to opioid receptors on nerve cells.
Their studies, conducted in mice and in cell lines expressing the opioid receptor, indicate that the modified drug still is an effective pain reliever but likely doesn’t have as many potentially deadly side effects. The research is published Nov. 30 in the journal Nature.
Although more studies are needed in additional animal models and in people to evaluate the strategy of modifying fentanyl, the research holds promise for developing safer opioid drugs that also relieve pain.
“Opioids, including fentanyl, are among the most effective pain-relieving drugs we have, but they also have led to too many accidental deaths, a situation that is simply tragic,” said the paper’s corresponding author, Susruta Majumdar, PhD, an associate professor of anesthesiology at Washington University and an associate professor of medicinal chemistry & pharmacology at the University of Health Sciences & Pharmacy. “We are desperately looking for ways to maintain the analgesic effects of opioids, while avoiding dangerous side effects such as addiction and respiratory distress that too often lead to death. Our research is still in its early stages, but we’re excited about its potential for leading to safer pain-relieving drugs.”
Fentanyl commonly is used to manage severe pain in cancer patients and in patients undergoing major surgery. It is up to 50 times stronger than heroin and 100 times stronger than morphine, and designer fentanyls often are sold on the street mixed with other drugs, such as heroin and oxycodone. More than 150 people die in the U.S. every day of overdoses related to opioid drugs such as fentanyl.