Oxycodone Hydrochloride

– Preferential MOP agonists such as oxycodone are often required for effective management of moderate to severe pain but come with significant risks of addiction and overdose – – With Dual NMR agonists, NOP and MOP agonism combine to provide analgesia while NOP counters many of the negative effects of MOP receptor agonism – – Dual NOP-MOP agonists have the potential to provide comparable analgesia, but with a substantially lower risk of abuse, addiction, and overdose than preferential MOP agonists such as oxycodone – MONMOUTH JUNCTION, N.J., Jan. 08, 2026 (GLOBE NEWSWIRE) -- Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced the acceptance of its peer-reviewed article “The Therapeutic Potential of Dual-NMR (NOP/MOP) Agonism in Pain Management” for publication in Pain and Therapy. Since its discovery in 1995, the nociception / orphanin FQ (NOP) receptor system has been an area of intense research. This paper presents the current state of understanding of the NOP receptor system and its interplay with the μ-opioid (MOP) receptor system. Additionally, the paper discusses the data that has been generated on a new class of dual NOP/MOP (dual-NMR) analgesics which has the promise of providing potent analgesia with a significantly lower risk of negative side effects associated with preferential MOP agonists such as oxycodone or morphine. Key findings from the publication include: Preferential MOP agonists, like morphine and oxycodone, are often the only effective treatments for moderate-to-severe pain, yet carry significant risks including physical dependence, tolerance, addiction, and respiratory depressionDespite sharing partial structural homology to opioid receptors, the NOP receptor has a distinct pharmacological profile: its activation produces analgesia while minimizing several side effects associated with MOP-only activationDual-NMR receptor agonists, which simultaneously activate both NOP and MOP receptors, have been designed to combine the pain-relieving benefits of both NOP and MOP activation, while mitigating many of the negative effects of preferential MOP agonism, offering a more balanced approach to pain managementStudies show that dual-NMR agonists provide strong analgesia across various pain types with a lower risk of physical dependence, tolerance, addiction, and respiratory depression, highlighting them as a promising new class that may provide effective pain management with a more balanced safety profile “Since its discovery 30 years ago, our understanding of the nociceptin system has grown,” said Dr. Roberto Ciccocioppo, PhD, Professor of Pharmacology at the University of Camerino and an author of the paper. “NOP receptor stimulation was first seen to provide analgesia, then discovered to counter many of the effects of MOP receptor stimulation, and now many studies across multiple compounds have shown that coactivation of NOP and MOP can provide strong analgesia with lower risks of serious side effects than MOP receptor stimulation alone. As a result, I believe dual-NMR agonists represent an important new breakthrough in pain management.” Details of the Publication Title: The Therapeutic Potential of Dual-NMR (NOP/MOP) Agonism in Pain ManagementAuthors: Roberto Ciccocioppo, PhD, University of Camerino; Jeffrey Gudin, MD, University of Miami Miller School of Medicine; Charles Argoff, M.D., Albany Medical College; Ema Offidani, Ph.D., Tris Pharma; James C. Hackworth, Ph.D., Tris Pharma; David Fam, Pharm.D., Tris Pharma; Jim Potenziano, Ph.D., Tris PharmaJournal: Pain and Therapy Tris Pharma commissioned this research in support of its work developing cebranopadol, a first-in-class investigational dual-NMR agonist. About Acute PainAcute pain affects millions of patients each year and is caused by injury, surgery, illness, trauma, burns or painful medical procedures, which can last up to three months, and typically resolves once the underlying cause is treated or healed. Moderate-to-severe acute pain can often only be effectively treated with opioid analgesics such as oxycodone, especially following joint replacements and other orthopedic procedures, invasive surgeries, and major traumas and burns. About Cebranopadol Cebranopadol is a first-in-class investigational therapy that targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors (a dual-NMR agonist), for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). These receptors are partially homologous to each other, and they play both complementary and distinct roles to modulate pain biology pathways. Studied in over 33 clinical trials in more than 2,200 subjects, cebranopadol’s profile has been well characterized in pain management studies. It has demonstrated positive clinical results in acute pain, chronic pain and diabetic neuropathic pain with a favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it could become the first dual-NMR pain-relief therapy with the potential to provide efficacy equivalent to selective MOP agonists such as oxycodone with less risk of misuse or physical dependence, addiction or overdose. Cebranopadol’s novel mechanism of action has potential in treating patients with substance use disorders (SUDs). Tris plans to continue to evaluate cebranopadol’s potential to help patients break the cycle of opioid addiction. The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has awarded Tris a five-year grant of up to $16.6 million to study cebranopadol’s potential to treat OUDs and SUDs. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris markets a portfolio of best-in-class ADHD products and is developing a promising pipeline of differentiated near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @TrisPharma. Media Contact Jonathan PappasLifeSci Communicationjpappas@lifescicomms.com Company Contact Cheryl PatnickTris Pharma, Inc.cpatnick@trispharma.com

Researchers at USF Health have discovered a new way opioid receptors can work that may lead to safer pain medications. Their findings show that certain experimental compounds can amplify pain relief without intensifying dangerous side effects like suppressed breathing. This research offers a fresh blueprint for designing opioids that last longer, work better, and pose fewer risks. It also opens doors to safer treatments for other brain disorders.Scientists at USF Health are making major progress in understanding how new opioid compounds interact with the body to relieve pain. Their work is raising optimism that future pain medications could deliver relief without the life-threatening side effects associated with today's opioids. Their latest findings were published December 17 in Nature under the title "GTP release-selective agonists prolong opioid analgesic efficacy." A companion study, "Characterization of the GTPγS release function of a G protein-coupled receptor," appeared the same day in Nature Communications. "Our overarching research aims to understand how opioids work so that we can ultimately provide safer options for chronic pain and develop therapies for opioid use disorders," said senior author Laura M. Bohn, PhD, senior associate dean for Basic and Translational Research and professor of Molecular Pharmacology and Physiology at the USF Health Morsani College of Medicine. How Opioids Relieve Pain and Cause Harm The studies focus on a group of experimental pain-relieving compounds that act on mu opioid receptors. These receptors are proteins found on nerve cells that reduce pain signals when activated by opioids such as morphine. However, activating these receptors also triggers serious side effects. Drugs like morphine can slow breathing, a dangerous effect that contributes to overdose deaths. Dr. Bohn and her team are working to develop compounds that ease pain without causing these harmful reactions. Their research reveals previously unknown ways opioid receptors behave when different drugs bind to them. New Insights Into Receptor Behavior Although the research is not expected to produce a new medication right away, it significantly improves scientific understanding of how receptors function, said Edward Stahl, PhD, assistant professor of Molecular Pharmacology and Physiology at the Morsani College of Medicine and a corresponding author on the study, which received funding from the National Institutes of Health. "Our manuscripts describe a unique way that drugs can control receptors," Dr. Stahl said. "Fundamentally, knowing more about how receptors work is the first step in understanding how to drug them and how to drug them safer. If this research is further validated, it would add to our textbook knowledge of how receptors function and, more importantly, to our ability to treat human health and disease." Reversing the Opioid Signal When opioids bind to a receptor, they trigger a sequence of events inside the cell that leads to pain relief and side effects. Long-term use of drugs such as morphine, oxycodone, and fentanyl often results in tolerance and dangerous breathing suppression. The researchers discovered that the earliest step in this signaling process can move in reverse. Some compounds appear to favor this backward reaction instead of pushing the process forward. "We've found that the first step of the chain reaction is reversible, and that some drugs can favor a reverse reaction over the forward reaction," Dr. Bohn said. "We've studied two new chemicals that strongly favor the reverse cycle and, when administered at non-effective doses, can enhance morphine and fentanyl-induced pain relief while not enhancing the respiratory suppression effects." Promising Frameworks, Not Final Drugs The newly studied molecules are not considered drug candidates. At higher doses, they still suppress breathing and have not undergone testing for toxicity or other opioid-related side effects. Even so, they provide valuable guidance for future drug design. "They do provide the framework for building new drugs," Dr. Bohn said. Building on Earlier Breakthroughs Dr. Bohn's laboratory previously identified a compound known as SR-17018. Unlike traditional opioids, SR-17018 does not cause breathing suppression or tolerance. It activates the same opioid receptor targeted by morphine, oxycodone, and fentanyl, but it attaches in a different way that leaves the receptor available for the body's own natural pain-relieving chemicals. While SR-17018 also favors the reverse signaling direction, researchers believe other features contribute to its improved safety profile. "For this reason," Dr. Bohn said, "we will be using our new findings to improve upon SR-17018." Broader Implications Beyond Pain Relief The research could influence drug development beyond opioids. Other receptors, including the serotonin 1A receptor, may also be activated in a reverse direction. According to Dr. Bohn, "this is an important drug target in neuropsychiatric disorders, including depression and psychosis." Context Within the Opioid Crisis These discoveries arrive amid an ongoing public health emergency linked to opioid misuse. Data show that opioids were involved in 68 percent of overdose deaths in 2024, with fentanyl and other synthetic opioids accounting for 88 percent of those fatalities. Dr. Bohn, an internationally recognized expert in molecular pharmacology and neurobiology, recently joined USF Health. She is widely known for her groundbreaking research on G protein-coupled receptors (GPCRs), the largest class of drug targets in the human body. Her lab has played a key role in revealing how selective signaling at opioid receptors can reduce pain without causing breathing suppression or tolerance. These findings deepen scientific understanding of opioid biology and move researchers closer to developing safer, non-addictive pain treatments.