31MAR

Welcome To Mediterr J Med Med Sci

Manuscripts are accepted for consideration with understanding that they are represent original material and they are not being considered for publication elsewhere. The editors welcome the submission of relevant articles for editorial consideration. Manuscripts and all scientific and professional data should be addressed to Editor-in-Cheif (Fathisherif@gmail.com).

Mediterranean Journal of Medicine and Medical Sciences
https://mmj.org.ly/article/doi/10.5281/zenodo.18310351

Mediterranean Journal of Medicine and Medical Sciences

Commentary Pharmacology

First-in-class non-opioid analgesics: Molecular mechanisms and clinical impact of suzetrigine

Rafsan Sium

Downloads: 1
Views: 164

Abstract

Effective and safe pain management remains a challenge for clinicians and researchers, despite the fact that pain is one of the most common and important clinical challenges in medicine. Despite their well-established risks of addiction, tolerance, respiratory depression, and a host of other negative effects, opioid analgesics continued to be the standard treatment for moderate to severe pain for many years. Recent scientific discoveries and regulatory initiatives have encouraged the creation of non-opioid analgesics with unique modes of action. As the first in a new class of non-opioid, peripherally acting painkillers approved by the U.S. Food and Drug Administration in 2025, suzetrigine, marketed as Journavx-represents a significant milestone. This article synthesizes current knowledge on the pharmacology, molecular mechanism, clinical efficacy, safety, and potential impact of suzetrigine in pain management.

Keywords

Analgesic, clinical effect, NaV1.8 sodium channel, pain, suzetrigine

References

  1. Mills SEE, Nicolson KP, Smith BH. Chronic pain: A review of its epidemiology and associated factors in population-based studies. British Journal of Anesthesia. 2019; 123(2): e273-e283. doi: 10.1016/j.bja.2019.03. 023
  2. Syed Nizamuddin SF. Xylazine-fentanyl crisis in North America: Epidemiology, clinical impact, and harm reduction. Mediterranean Journal of Medicine and Medical Sciences. 2025; 1(2): 32-36. doi: 10.5281/zenodo. 17058720
  3. Schafer-Kavvadias S. Improvement of opioid addiction medication through extended-release naltrexone: a comparative, experimental, and laboratory approach. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2023; 3(1): 3-5. doi: 10.5281/zenodo.7771314
  4. Preuss CV, Kalava A, King KC. Prescription of controlled substances: Benefits and risks. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025; PMID: 30726003. Bookshelf ID: NBK537318.
  5. Cunico D, Rossi A, Verdesca M, Principi N, Esposito S. Pain management in children admitted to the emergency room: A narrative review. Pharmaceuticals. 2023; 16(8): 1178. doi: 10.3390/ph16081178
  6. Akter B, Aishee S, Hridoy A, Pulok MMH, Islam MA, Biswas A, et al. Structural tailoring of etoricoxib: A spectrochemical, medicinal and pharmacological study. Chemical Physics Impact. 2025; 10: 100830. doi: 10.1016/j.chphi.2025.100830
  7. Shallof NM, Abduelkarem AR. Suzetrigine mechanism, efficacy, and clinical implications: A narrative review. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2025; 5(4): 90-95. doi: 10.5281/zenodo. 18008693
  8. The U.S. Food and Drug Administration. FDA approves novel non-opioid treatment for moderate to severe acute pain. 2025; press announcement. For Immediate Release: January 30, 2025.
  9. Mackieh R, Abou-Nader R, Wehbe R, Mattei C, Legros C, Fajloun Z, Sabatier JM. Voltage-gated sodium channels: A prominent target of marine toxins. Marine Drugs. 2021; 19(10): 562. doi: 10.3390/md19100562
  10. Heinle JW, Dalessio S, Janicki P, Ouyang A, Vrana KE, et al. Insights into the voltage-gated sodium channel, NaV1.8, and its role in visceral pain perception. Frontiers in Pharmacology. 2024; 15: 1398409. doi: 10.3389/ fphar.2024.1398409
  11. Hameed S. Nav1.7 and Nav1.8: Role in the pathophysiology of pain. Molecular Pain. 2019; 15: 1744806919 858801. doi: 10.1177/1744806919858801
  12. Rai MA, Bhat R, Shabaraya. Knowledge, attitudes, and practice of pharmacists in opioid abuse prevention: A cross-sectional study in Mangalore, India. Mediterranean Journal of Medical Research. 2025; 2(2): 38-44. doi: 10.5281/zenodo.15455698
  13. Jones J, Correll DJ, Lechner SM, Jazic I, Miao X, Shaw D, et al. VX21-548-101 and VX21-548-102 trial groups. Selective inhibition of NaV1.8 with VX-548 for acute pain. The New England Journal of Medicine. 2023; 389(5): 393-405. doi: 10.1056/NEJMoa2209870
  14. McCoun J, Winkle P, Solanki D, Urban J, Bertoch T, Oswald J, et al. Suzetrigine, a non-opioid NaV1.8 inhibitor with broad applicability for moderate-to-severe acute pain: A phase 3 single-arm study for surgical or non-surgical acute pain. Journal of Pain Research. 2025; 18: 1569-1576. doi: 10.2147/JPR.S509144
  15. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Sciences Policy; Committee on Pain Management and Regulatory Strategies to Address Prescription Opioid Abuse; Phillips JK, Ford MA, Bonnie RJ, editors. Pain management and the opioid epidemic: Balancing societal and individual benefits and risks of prescription opioid use. Washington (DC): National Academies Press (US); 2017; 2: Pain Management and the Intersection of Pain and Opioid Use Disorder: Bookshelf ID: NBK458655
  16. Kaneko Y, Szallasi A. Transient receptor potential (TRP) channels: A clinical perspective. British Journal of Pharmacology. 2014; 171(10): 2474-507. doi: 10.1111/bph.12414
  17. Schumacher MA. Transient receptor potential channels in pain and inflammation: Therapeutic opportunities. Pain Practice. 2010; 10(3): 185-200. doi: 10.1111/j.1533-2500.2010.00358.x
  18. Hoque M. Mechanisms, clinical implications, and treatment strategies for autonomic health dysfunction in anxiety and depression. Batna Journal of Medical Sciences. 2025; 12(4): 28. doi: 10.48087/BJMSoa.2025. 12428
  19. Osteen JD, Immani S, Tapley TL, Indersmitten T, Hurst NW, Healey T, et al. Pharmacology and mechanism of action of suzetrigine, a potent and selective NaV1.8 pain signal inhibitor for the treatment of moderate to severe pain. Pain Therapy. 2025; 14(2): 655-674. doi: 10.1007/s40122-024-00697-0
  20. Keam SJ. Suzetrigine: First approval. Drugs. 2025; 85(6): 845-851. doi: 10.1007/s40265-025-02178-w
  21. Rajasingham R, Qi Y. Suzetrigine, a non-opioid small-molecule analgesic: Mechanism of action, clinical, and translational science. Clinical and Translational Sciences. 2025; 18(11): e70414. doi: 10.1111/cts.70414
  22. Harrison C. Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels. WIPO (PCT), WO: WO2022256660A1. 8-12-2022.
  23. Zhu F, Qin H. Shandong Fuchang Pharmaceutical Co., Ltd. Preparation method of suzetrigine. CN118772124A, 15-10-2024.
  24. Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, et al. Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. Nature. 2016; 534(7608): 494-499. doi: 10.1038/nature17976
  25. Kingwell K. NaV1.8 inhibitor poised to provide opioid-free pain relief. Nature Reviews of Drug Discovery. 2025; 24(1): 3-5. doi: 10.1038/d41573-024-00203-3
  26. McCormack K, Santos S, Chapman ML, Krafte DS, Marron BE, West CW, et al. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels. Proceedings of the National Academy of Sciences USA. 2013; 110(29): E2724-32. doi: 10.1073/pnas.1220844110
  27. Wang H, Huang J, Zang J, Jin X, Yan N. Drug discovery targeting Nav1.8: Structural insights and therapeutic potential. Current Opinion in Chemical Biology. 2024; 83: 102538. doi: 10.1016/j.cbpa.2024.102538 Erratum in: Current Opinion in Chemical Biology. 2025; 84: 102546. doi: 10.1016/j.cbpa.2024.102546
  28. ClinicalTrials.gov, Evaluation of the Long-term Safety and Effectiveness of Suzetrigine (SUZ) in participants with painful Diabetic Peripheral Neuropathy (DPN), Clinical Trials. gov Identifier: NCT06696443.
  29. Yale Medicine. CARRIE MACMILLAN February 21, 2025. https://www.yalemedicine.org/news/new-non-opioid-pain-pill?utm_source=chatgpt.com  (Accessed 20 December 2025).
  30. Vertex Pharmaceuticals [Internet], Vertex Announces Results From Phase 2 Study of Suzetrigine for the Treatment of Painful Lumbosacral Radiculopathy (Vertex Pharmaceuticals, 2024).

Submitted date:
11/02/2025

Reviewed date:
01/11/2026

Accepted date:
01/20/2026

Publication date:
01/20/2026

696f4307a953951c00698a3b mjmmr Articles
Links & Downloads

Mediterr J Med Med Sci

Share this page
Page Sections