Salt could help scientists develop a safer version of fentanyl

‘In its current form, fentanyl is like a weapon of mass destruction.’

LOS ANGELES — More salt may not be such a bad thing after all. Researchers from Washington University in St. Louis and Stanford University say that sodium may be the secret ingredient in developing safer opioids for pain relief.

Opioid overdoses took the lives of almost 70,000 Americans in 2020, mostly attributed to synthetic painkillers and fentanyl. The Food and Drug Administration (FDA) approved fentanyl use for cancer patients experiencing persistent, severe pain in the 1990s. Unfortunately, the drug has made its way to the streets, where it’s regularly abused and distributed illegally.

“In its current form, fentanyl is like a weapon of mass destruction,” says corresponding author Vsevolod Katritch, a computational scientist from the Bridge Institute at USC Michelson Center for Convergent Bioscience, in a university release. “Our new collaborative work suggests that we could redesign the drug in such a way that we convert this frequent overdose killer to a much more benign but still effective analgesic.”

How do opioids act on the body’s nerves?

Katritch and his team have studied sodium’s potential to create safer medications since they first found it in adenosine and opioid receptors over 10 years ago. Their newest molecular-focused work conducted on mice supports their views that sodium could block the harmful effects of opioid drugs.

Drug manufacturers design pain relievers to target specific receptors on nerve cells called GPCRs, or G-protein coupled receptors, which function as signaling transmitters. They act like switches that help the drug act as intended on the brain and body. Unfortunately, they can also cause unwanted side-effects. Fentanyl, one of the strongest and dangerous opioids available, can lead to addiction or cause fatal overdoses by inducing respiratory arrest.

“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,” says corresponding author Susruta Majumdar from Washington University. “Our research is still in its early stages, but we’re excited about its potential for leading to safer pain-relieving drugs.”

This work paves the way for presenting a new molecular design concept for dozens of other GPCRs and drugs that may come with significant, and possibly life-threatening side-effects. Their studies also may encourage scientists to continue their efforts in working toward safer usage of painkillers as they are currently designed.

While Katritch and the team agree that their findings regarding sodium are strong, they also emphasize that further studying is imperative before they can prove that this produces a less harmful-yet-effective alternative to fentanyl and other drugs in clinical care settings.

The findings appear in the journal Nature.

About the Author

Shyla Cadogan

Shyla Cadogan is a recent graduate from the University of Maryland, College Park with a Bachelor’s of Science in Nutrition and Food Science. She is on her way to becoming a Registered Dietitian, with next steps being completion of a dietetic internship at the University of Maryland Medical Center where she currently is gaining experience with various populations and areas of medical nutrition such as Pediatrics, Oncology, GI surgery, and liver and renal transplant. Shyla also has extensive research experience in food composition analysis and food resource management.

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