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A Safer Opioid? Scientists Are Onto Something

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The most abundant element on Earth — sodium — could hold the key to scientists developing opioids or other drugs with far fewer side effects.

In a study published on Wednesday naturescientists from the University of Southern California, Washington University in St. Louis, and Stanford University demonstrated that by combining fentanyl with sodium Found in pockets inside nerve cell receptors, they can block harmful side effects of drugs and still reduce pain.

Further research is needed, but the results are promising — not just for drug development It’s about addressing the nation’s addiction and overdose crisis. According to the National Institute on Drug Abuse, nearly 70,000 Americans died from opioid overdoses in 2020 — mostly from the synthetic opioid fentanyl. In the 1990s, the U.S. Food and Drug Administration approved the use of fentanyl for severe pain relief cancer patientBut it has taken to the streets, fueling a national opioid crisis.

“In its current form, fentanyl is like a weapon of mass destruction,” said Vsevolod Katritch, a computational scientist at the Bridge Institute at the USC Michelson Center for Convergent Biosciences and the study’s corresponding author. “Our new collaborative work shows that we can redesign drugs to convert this frequent overdose killer into a milder but still effective pain reliever.”

Drugs of all classes are designed to target specific receptors nerve cell Known as GCPR, or G-coupled protein receptor, acts as a signal transmitter.These receptors act like switches, mediating drugExpected effects on the brain and body, but also unexpected side effects. In the case of fentanyl, the most potent painkiller of all opioids, patients can become addicted and may die from respiratory arrest.

Katritch noted that since their first use of adenosine and opioid receptor about ten years ago.

Katritch and his collaborators say that while further research is needed to prove that their less harmful version of fentanyl works in humans, the findings open a new door for scientists to potentially improve the painkiller’s efficacy. safety.

“We are desperately searching for ways to maintain the analgesic effects of opioids while avoiding dangerous side effects, such as addiction and respiratory distress, which often lead to death,” said corresponding author Susruta Majumdar of Washington University in St. Louis. “Our research is still in its early stages, but we’re excited about its potential to develop safer pain medications.”

Exceed opioids receptors, Katritch noted, and that this work opens up a new concept of molecular design for many other GPCRs where such a switch of function in existing drugs is desirable.

More information:
Abdelfattah Faouzi et al., Structure-Based Design of Dual Ligands for the μ-Opioid Receptor, nature (2022). DOI: 10.1038/s41586-022-05588-y

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Safer opioids? Scientists are working on something (November 30, 2022)
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