Summary: A new experimental drug, SBI-810, may deliver potent pain relief without the addictive and harmful side effects of opioids.
Unlike opioids, SBI-810 precisely targets a single brain receptor pathway linked to pain reduction, avoiding the euphoric “high” and dangerous complications.
“It’s a promising target for treating acute and chronic pain.” SBI-810 effectively relieved pain from surgical incisions, bone fractures, and nerve injuries better than some existing painkillers.
Here, we demonstrate that its analog, SBI-810, exhibits potent antinociceptive properties in rodent models of postoperative pain, inflammatory pain, and neuropathic pain via systemic and local administration.
These findings highlight NTSR1-biased allosteric modulators as a promising, non-addictive therapeutic strategy for acute and chronic pain management, acting through both peripheral and central mechanisms.
In conclusion, SBI-810, a novel experimental medication, may provide effective pain relief without the negative and addictive side effects of opioids. In contrast to opioids, SBI-810 avoids the euphoric “high” and harmful side effects by specifically targeting a single brain receptor pathway associated with pain reduction.
The medication successfully reduced pain in mice following surgery, fractures, and nerve damage. It even improved the effects of opioids at lower dosages without producing tolerance. It also worked better than existing drugs like gabapentin without causing drowsiness or memory issues. By using a method known as biased agonism to activate neurotensin receptor 1, SBI-810 provides pain relief via a more secure signaling pathway.
Key Facts:.
Precision targeting: SBI-810 does not impact pathways linked to addictive opioids, but it does activate a single pain-relieving pathway (β-arrestin-2).
No Sedation or Tolerance: Mice given SBI-810 did not exhibit typical side effects like sedation or memory loss, nor did they develop tolerance.
Enhanced Effectiveness: SBI-810 increased opioid effects at lower, safer doses and decreased pain from a variety of sources.
Duke University serves as the source.
Strong pain relief without the harmful side effects of opioids may be possible with an experimental medication created at Duke University School of Medicine.
The medication, SBI-810, belongs to a new class of substances that are intended to target a spinal cord and nerve receptor. Opioids randomly flood many cellular pathways, but SBI-810, a non-opioid treatment, adopts a more targeted strategy by only activating a particular pain-relieving pathway, avoiding the euphoric “high” associated with addiction.
The study, published May 19 in Cell, found that SBI-810 performed well alone in mouse tests and that when combined, it increased the effectiveness of opioids at lower dosages.
“This compound is exciting because it is both analgesic and non-opioid,” said Ru-Rong Ji, PhD, a senior study author and researcher in neurobiology and anesthesiology who leads the Duke Anesthesiology Center for Translational Pain Medicine.
Even better, it avoided common side effects like constipation and tolerance building, which over time often forces patients to require higher and more frequent doses of opioids.
While SBI-810 is still in the early stages of development, Duke researchers have already secured several patents for the discovery and hope to soon begin human trials.
Alternative methods of pain relief are desperately needed. Despite a decrease in drug overdose deaths, opioids continue to be the leading cause of death for over 80,000 Americans annually. A third of Americans suffer from chronic pain. S. . inhabitants.
According to researchers, the medication might be a safer choice for people recovering from surgery or dealing with diabetic nerve pain, as it can treat both acute and chronic pain.
The purpose of SBI-810 is to target neurotensin receptor 1 in the brain. It uses a technique called biased agonism to turn on β-arrestin-2, a signal associated with pain relief, while blocking other signals that may result in addiction or negative side effects.
According to Ji, “sensory neurons as well as the brain and spinal cord express the receptor.”. “It is a promising target for the treatment of both chronic and acute pain.”. “”.
More effectively than some current painkillers, SBI-810 reduced pain from surgical incisions, bone fractures, and nerve injuries. When administered to mice, it decreased facial grimacing and guarding, two indicators of impulsive discomfort.
In some circumstances, SBI-810 performed better than oliceridine, a more recent opioid used in hospitals, according to Duke researchers, who also observed fewer symptoms of distress.
SBI-810 did not lead to tolerance after repeated use, in contrast to opioids like morphine. Additionally, it worked better than gabapentin, a common medication for nerve pain, and it didn’t cause sedation or memory issues, which are common side effects of gabapentin.
The compound’s dual action on the central and peripheral nervous systems, according to researchers, may provide a new kind of balance in pain management: potent enough to be effective but precise enough to prevent damage.
Finances: The Department of Defense and the NIH provided funding for the study.
The first authors, Ran Guo and Ouyang Chen, are joined by Sangsu Bang, Sharat Chandra, Yize Li, Gang Chen, Rou-Gang Xie, Wei He, Jing Xu, Richard Zhou, Shaoyong Song, Ivan Spasojevic, and Marc G among other Duke authors. Caron, William C. Lawrence S. Barak and Wetsel.
Regarding this news about neuropharmacology research.
Written by Shantell Kirkendoll.
Duke University serves as the source.
Contact: Duke University’s Shantell Kirkendoll.
Picture: The picture is from Neuroscience News.
Original Study: Publicly available.
According to Ru-Rong Ji et al., “Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain.”. cell.
Abstract.
Neurotensin receptor 1 is an arrestin-biased allosteric modulator that reduces both acute and chronic pain.
By avoiding β-arrestin-2 (βarr2) signaling, G-protein-biased agonists have been demonstrated to improve opioid analgesia.
SBI-553, an allosteric modulator biased toward βarr2 signaling and positive for neurotensin receptor 1 (NTSR1), has been shown to reduce the effects of psychostimulants in mice.
By administering SBI-810 systemically and locally, we show that its analog has strong antinociceptive effects in rodent models of neuropathic pain, inflammatory pain, and postoperative pain. The analgesic effects of SBI-810 depend on βarr2 and NTSR1 but not on βarr1 or NTSR2.
The mechanism by which SBI-810 works is as follows: it dampens C-fiber responses, suppresses excitatory synaptic transmission, inhibits NMDA receptor and extracellular-regulated signal kinase (ERK) signaling in spinal cord nociceptive neurons, and decreases Nav1.7 surface expression and action potential firing in primary sensory neurons.
In terms of behavior, it lessens constipation, opioid-induced conditioned place preference, and chronic opioid withdrawal symptoms.
These results demonstrate that NTSR1-biased allosteric modulators, which work through both peripheral and central mechanisms, represent a promising non-addictive therapeutic approach for the treatment of acute and chronic pain.
