Experimental drug could provide pain relief without the side effects of opioids

Experimental drug could provide pain relief without the side effects of opioids

An experimental drug developed at Duke University School of Medicine could provide powerful pain relief without the dangerous side effects of opioids.

The drug, called SBI-810, is part of a new generation of compounds that target a receptor on the nerves and spinal cord. While opioids flood multiple cellular pathways indiscriminately, SBI-810, a non-opioid treatment, takes a more focused approach and activates only a specific pain relief pathway, avoiding the euphoric “high” associated with addiction.

In tests in mice, SBI-810 worked well on its own and in combination made opioids more effective at lower doses, according to the study published May 19 incell.

“What makes this compound exciting is that it is both analgesic and non-opioid,” said senior study author Ru-Rong JI, PhD, an anesthesiology and neurobiology researcher who directs the Duke Anesthesiology Center for Translational Pain Medicine.

Even more encouraging, it prevented common side effects like constipation and tolerance building that often force patients to require stronger and more frequent doses of opioids over time.

SBI-810 is in early development, but Duke researchers are moving toward human trials soon and they have locked up several patents for the discovery.

There is an urgent need for alternatives to pain relief. Drug overdose deaths are falling, but more than 80,000 Americans still die each year from opioids. Chronic pain now affects one-third of the U.S. population.

Researchers said the drug could be a safer option to treat both short-term and chronic pain for those recovering from surgery or living with diabetic nerve pain.

SBI-810 is designed to target the brain receptor neurotensin receptor. Using a method called biased agonism, it switches on a specific signal β-arrestin-2 to relieve pain and avoids other signals that can cause side effects or addiction.

The receptor is expressed on sensory neurons as well as the brain and spinal cord. It is a promising target for the treatment of acute and chronic pain. “

Ru-Rong JI, PhD, anesthesiology and neurobiology researcher

SBI-810 effectively relieved pain from surgical incisions, bone fractures and nerve injuries better than some existing painkillers. When injected into mice, it reduced signs of spontaneous discomfort, such as facial guarding and grimacing.

Herzog scientists compared SBI-810 with oliceridine, a newer type of opioid used in hospitals, and found that SBI-810 worked better in some situations, with fewer signs of distress.

Unlike opioids such as morphine, SBI-810 did not cause tolerance after repeated use. It also outperformed gabapentin, a common nerve pain medication, and did not cause sedation or memory problems commonly seen with gabapentin.

Researchers said the compound's dual action on both the peripheral and central nervous systems could offer a new kind of balance in pain medicine: powerful enough to work but specific enough to prevent harm.

The study was supported by the NIH and the Department of Defense.

Other Herzog authors include the first authors who pursued Guo and Ouyang Chen. Sangsu Bang, Sharat Chandra, Yize Li, Gang Chen, Rou-Gang Xie, Wei, Jing Xu, Richard Zhou, Shaoyong Song, Ivan Spasojevic, Marc G. Caron, William C. Wetsel, and Lawrence S. Barak.

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