Majumdar Publishes Breakthrough Opioid Research in Nature
Published on 30 November 2022
Groundbreaking research conducted by Susruta Majumdar, Ph.D., associate professor of medicinal chemistry and pharmacology at University of Health Sciences and Pharmacy in St. Louis, and his colleagues, has identified a method for modifying the chemical properties of the opioid pain reliever, fentanyl, and altering how it binds to opioid receptors on nerve cells.
Through studies conducted in cell lines expressing the opioid receptor and in mice, the modified version of fentanyl was found to be an effective pain reliever with fewer significant side effects. The research, which was recently published in the journal Nature, offers potential avenues for the creation of safer opioid medications.
“Our research is still in the early stages, but we are hopeful that it can lead to the development of safer pain-relieving drugs down the road,” Majumdar explained. “Opioids, like fentanyl, are highly effective at relieving pain, but they come with dangerous side effects. Our goal is to create novel analgesics that can provide pain relief without the respiratory depression and addiction potential that exists with opioids, and our work to modify fentanyl appears to be a pathway in that direction.”
Majumdar's research team was comprised of collaborators from the Center for Clinical Pharmacology, along with 2012 Nobel Laureate Brian K. Kobilka, MD, Ph.D., chair of cardiology at Stanford Medicine; Vsevolod Katritch, Ph.D., associate professor of quantitative and computational biology and chemistry at the University of Southern California; Georgios Skiniotis, Ph.D., professor of molecular and cellular physiology and structural biology at Stanford University and Jay P. McLaughlin, professor of pharmacodynamics at University of Florida.
Through their research, the team developed a variation of fentanyl that could bind to mu receptors on nerve cells and engaged a sodium ion binding site that was present within the receptor.
“What we found was that by engaging the sodium binding site as a target, we were able to slightly alter the pathway through which fentanyl acts to combat pain, making it possible for the drug to maintain most of its pain-relieving effects, while also reducing adverse side effects like respiratory distress,” Majumdar said. “While the idea that the sodium ion could modulate opioid receptors isn’t new, our team appears to be the first to successfully alter the chemistry of fentanyl so that it interacts with the sodium site on the receptor.”
Majumdar adds that this breakthrough has the potential to help reduce the side effects associated with drugs beyond opioids.
“Almost one-third of medications targeting G-protein coupled receptors that are currently on the market could be modified to be more effective with fewer side effects through the modulation of the sodium binding site present in these targets,” Majumdar said. “Our research offers many new avenues for future discovery, and our team is thrilled to be able to make this exciting contribution to the greater scientific community.”
View the full text of Majumdar’s Nature paper.
Majumdar’s research is conducted through the Center for Clinical Pharmacology. Established in 2015, the Center for Clinical Pharmacology is a partnership between University of Health Sciences and Pharmacy in St. Louis and the Department of Anesthesiology at Washington University School of Medicine in St. Louis. The center continues to diversify with faculty investigators currently engaged in a variety of diverse research areas.