Summary: A new experimental medication, SBI-810, can offer a relief of powerful pain without the addictive and harmful side effects of opioids. Unlike opioids, SBI-810 targets precisely a single cerebral receiver route linked to the reduction of pain, avoiding euphoric and dangerous “high” complications.
In mice, the drug has actually relieved the pain of surgery, fractures and nerve damage, and even improved the effects of opioids in lower doses without causing tolerance. He also outperformed current drugs such as gabapentine without inducing sedation or memory problems. SBI-810 works by activating the neurotensin 1 receiver using a technique called biased agonism, offering pain relief through a safer signaling route.
Key facts:
- Precision targeting: SBI-810 Activates a single pain of pain discharge (β-Arrestin-2) without affecting paths linked to addictive opioids.
- No tolerance or sedation: The mice treated with SBI-810 have not developed tolerance or do not feel common side effects such as sedation or memory loss.
- Increased efficiency: SBI-810 has reduced pain from various sources and increased the effects of opioids in safer and safer doses.
Source: Duke University
An experimental drug developed at the Duke University School of Medicine could offer a powerful relief of pain without the dangerous side effects of opioids.
The drug, called SBI-810, is part of a new generation of compounds designed to target a receiver on the nerves and the spinal cord. While opioids flood several cellular routes without discrimination, SBI-810, non-opioid treatment, adopts a more targeted approach, only activating a specific pain of pain that avoids the euphoric “high” related to dependence.
In mouse tests, the SBI-810 worked well alone and, when used in combination, made opioids more effective in lower doses, according to the study published on May 19 Cell.
“What makes this compound exciting is that it is both analgesic and not opioid,” said the author of the main study Ru-Rong Ji, PHD, anesthesiology and neurobiology researcher who directs the Duke Anesthesiology Center for Translational Pain Medicine.
Even more encouraging: he prevented common side effects such as constipation and accumulation of tolerance, which often requires patients to need stronger and more frequent opioid doses over time.
SBI-810 is at the start of development, but Duke’s researchers soon targeting human tests and they have locked several patents for the discovery.
There is an urgent need for alternative pain relief. Deaths by overdose of drugs decrease, but more than 80,000 Americans still die from opioids each year. Meanwhile, chronic pain affects a third of the American population.
Researchers said the drug could be a safer option to treat short -term and chronic pain for those who recover from surgery or live with diabetic nervous pain.
The SBI-810 is designed to target the neurotensin receptor of the cerebral receiver 1. Using a method known as biased agonism, it lights a specific signal-β-Arrestin-2-linked to pain relief, while avoiding other signals which can cause side effects or dependence.
“The receiver is expressed on sensory neurons and the spinal cord,” said JI. “It is a promising target for treating acute and chronic pain.”
SBI-810 has effectively relieved the pain of surgical incisions, bone fractures and nerve lesions better than certain existing pain relievers. When injected into mice, it reduced the signs of spontaneous discomfort, such as the guard and facial ignoring.
Duke scientists compared SBI-810 to oliridin, a new type of opioid used in hospitals, and found that SBI-810 was better in certain situations, with fewer signs of distress.
Unlike opioids like morphine, SBI-810 did not cause tolerance after repeated use. He also outperformed gabapentine, a common drug for nervous pain, and has not caused sedation or memory problems, which are often observed with gabapentine.
The researchers said that the double action of the compound – both on peripheral and central nervous systems – could offer a new type of balance in pain medicine: powerful enough to work, but specific enough to avoid damage.
Funding: The study was supported by the NIH and the Ministry of Defense.
Other Duke authors include the first authors Ran Guo and Ouyang Chen; Sangsu Bang, Sharat Chandra, Yize Li, Gang Chen, Rou-Gang Xie, Wei He, Jing Xu, Richard Zhou, Shaoyong Song, Ivan Spasojevic, Marc G. Caron, William C. Wettel and Lawrence S. Barak.
About this news of research in neuropharmacology
Author: Shantell kirkendoll
Source: Duke University
Contact: Shantell Kirkendoll – Duke University
Picture: The image is credited with Neuroscience News
Original search: Open access.
“The biased allosterical modulator of the neurotensin receptor 1 relieves acute and chronic pain” by Ru-Rong Ji et al. Cell
Abstract
Allosterical Modulator in Porestine of the neurotensin 1 receptor mitigates acute and chronic pain
It has been shown that agonists biased by G proteins improve the analgesia of opioids by bypassing the β-Arrestin-2 signaling (βarr2).
We previously reported that SBI-553, a positive allosterical modulator with biased neurotensin (NTSR1) to βarr2 signaling, reduces psychostimulant effects in mice.
Here, we will demonstrate that his analog, SBI-810, has powerful antinocceptive properties in models of postoperative pain, inflammatory pain and neuropathic pain via systemic and local administration. The analgesic effects of SBI-810 require ntsr1 and βarr2 but not ntsr2 or βar1.
Mechanically, SBI-810 eliminates the excitatory synaptic transmission, inhibits the signaling of the NMDA receptor and the signal kinase regulated by extracellular (ERK) in the nociceptive neurons of the spinal cord, reduced Nav1.7 Surface expression and potential action shooting in primary sensory neurons and covers the responses of fibers C.
In a behavioral manner, it reduces the preference for a placed place induced by opioids, reduces constipation and reduces chronic opioid withdrawal symptoms.
These results highlight biased allosteric modulators NTSR1 as a promising and non -addictive therapeutic strategy for acute and chronic pain management, acting both by peripheral and central mechanisms.
