Synthetic and semi-synthetic opioids offer powerful pain relief. Unfortunately, these drugs are also associated with negative outcomes, including addiction and overdose. The U.S. Centers for Disease Control and Prevention reported 48,422 deaths related to synthetic opioids in 2024. While this is a noted decrease from the 76,282 deaths that occurred in 2023, viable pain-relief alternatives are still an urgent need for the millions of individuals suffering from chronic pain. SBI-810, an experimental non-opioid drug developed at Duke University School of Medicine, could offer an alternative.
According to a study published May 19 in Cell, SBI-810 worked well on its own when used in mice. When used in combination with opioids, SBI-810 also made the drugs more effective — at much lower doses. Below, we’ve outlined the research, including the team’s hopeful next steps into human trials.
Identifying a Non-Opioid Alternative for Powerful Pain Relief
Opioids travel through the bloodstream, flooding multiple cellular pathways to target pain receptors. This indiscriminate flooding approach also impacts the reward system in the brain, leading to feelings of relaxation and euphoria that can drive opioid addiction. As a non-opioid treatment, SBI-810 takes a much more focused approach. The drug is designed to target a receptor on the nerves and spinal cord — a highly specific pain-relief pathway. This targeted approach is meant to avoid the “high” associated with opioids. This could make SBI-810 a safer choice for pain relief.
Experimental Drug Targets Specific Brain Receptor
SBI-810 is designed to target the brain receptor neurotensin receptor 1 (NTSR1), which regulates functions such as hypotension, hyperglycemia, hypothermia, and antinociception, or pain relief. The Duke team used biased agonism to “switch” on a signal within NTSR1. This technique elicits distinct responses from a receptor using ligands, or molecules that bind to specific receptors. The team targeted the β-arrestin-2 signal, which is linked to pain relief. The researchers then observed its pain-relief effects on mice.
Mouse Trials Offer Promising Results
In mouse subjects, injected SBI-810 was found to effectively relieve pain from surgical incisions, bone fractures, and nerve injuries better than some existing painkillers. For example, the scientists compared SBI-810 to the opioid oliceridine and found SBI-810 worked better in some situations. SBI-810 also reduced signs of spontaneous discomfort, such as facial grimacing.
Additionally, SBI-810 was tested for long-term drug tolerance. Unlike opioids like morphine, SBI-810 did not cause tolerance after repeated use. In other words, the drug was not rendered less effective after long-term use, and the scientists did not have to increase the subjects’ dosage for relief. The drug also prevented common side effects like constipation, potentially making it a viable long-term solution for pain.
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While opioids are highly effective pain relievers, they are also associated with significant adverse effects, including constipation, the development of tolerance, and a risk of addiction that may lead to overdose and potentially even death. SBI-810 could be a game-changer. Researchers called it “powerful enough to work, yet specific enough to avoid harm.” While the drug is still in early development, the team is aiming for human trials soon.
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