Unafra (opiranserin) / Vivozon - LARVOL DELTA

A Role for Glycine Transporter-2 Inhibitors in Regulating Accumbal Dopamine Levels and Voluntary Alcohol Intake in Rats. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Overall, this study indicates that synaptic GlyRs are involved in regulating nAc DA levels and alcohol intake in rats, but probably to a lesser extent than extrasynaptic GlyRs. Further studies that specifically target GlyT2 in, for example, the nAc and septal regions and that utilize refined techniques for measuring synaptic glycine levels are warranted to better characterize the role of glycinergic innervation in the reward circuitry and for regulating alcohol intake."

Journal • Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Opiranserin Injections PCA Regimens for Postoperative Pain (clinicaltrials.gov) - P2 | N=66 | Completed | Sponsor: Samsung Medical Center

New P2 trial • Pain

A role for glycine transporter 2-inhibitors in modulating levels of dopamine in the nucleus Accumbens (EAN 2026) - " The partial GlyT2-inhibitors NAGly (10 mg/kg i.p.) and Opiranserin (20 mg/kg i.p.), but not the full GlyT2-inhibitor Org 25543, slightly elevated accumbal DA levels, while no effects on extrasynaptic glycine levels were observed. The reversible GlyT1-inhibitor Bitopertin (10 mg/kg p.o.) produced a pronounced glycine and DA elevation but combined GlyT1- and GlyT2 inhibition did not yield any statistically significant additive effects... To conclude, this study indicates that GlyT2-expressing glycinergic neurons are involved in regulating nAc DA levels, albeit to a lesser extent than extrasynaptic GlyRs situated nearby GlyT1s. The extraspinal effects mediated by systemic treatment with GlyT2-inhibitors, i.e. involvement of the mesolimbic DA system, should be further explored."

Opiranserin for Minimally Invasive Cholecystectomy (clinicaltrials.gov) - P=N/A | N=88 | Recruiting | Sponsor: Gangnam Severance Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • Pain

Effects of opiranserin (Unafra) on mechanical nociceptive thresholds in Beagle dogs: a randomized crossover study. (PubMed, Vet Anaesth Analg) - "A 4-hour CRI of opiranserin (5 mg kg-1 hour-1) increased MNTs during infusion in dogs without clinically relevant sedation or cardiovascular depression. These findings are consistent with antinociceptive activity under this experimental model."

Journal • Anesthesia • Cardiovascular • CNS Disorders • Depression • Pain • Psychiatry

Opiranserin for Minimally Invasive Cholecystectomy (clinicaltrials.gov) - P=N/A | N=88 | Not yet recruiting | Sponsor: Gangnam Severance Hospital

Head-to-Head • New trial • Pain

Transport and inhibition mechanisms of human glycine transporter 2. (PubMed, Nat Commun) - "Both inhibitors, ORG25543 and opiranserin, bind to an allosteric site, which is vertical to the extracellular tunnel, buried under the extracellular loop 4 (EL4) and near to the transmembrane helix 1b (TM1b)...Further structural analysis reveals both global and local conformational changes associated with the ions and glycine binding and release. These structures define the mechanisms governing transport and allosteric inhibition in hGlyT2, providing a blueprint for further development of non-opioid analgesics targeting hGlyT2."

Journal • Pain

Mechanisms of transport and analgesic compounds recognition by glycine transporter 2. (PubMed, Proc Natl Acad Sci U S A) - "Furthermore, the complex structures with small compounds ALX1393, opiranserin, and ORG25543 reveal their competitive and allosteric inhibition mechanisms. Overall, our study provides a solid foundation for understanding glycine reuptake mechanisms and developing effective and safer analgesic agents."

Journal • Neuralgia • Pain

Opiranserin injection (Unafra®) as a first-in-class, non-opioid analgesic for the treatment of acute postoperative pain. (PubMed, Anesth Pain Med (Seoul)) - "In this review, we aim to describe the discovery and optimization of opiranserin through efficacy-based screening using a bait-target approach, outline its pharmacological mechanisms of action as a drug with both central and peripheral activity, and summarize published clinical studies demonstrating its successful translation from preclinical efficacy to reductions in postoperative pain and opioid consumption. We also discuss the clinical implications and future research directions to enhance the therapeutic utility of opiranserin injection and maximize patient benefit within the framework of precision analgesia."

Journal • Review • Pain

A role for Glycine Transporter-2 inhibitors in regulating accumbal dopamine levels and voluntary alcohol intake in rats (ECNP 2025) - " Effects on nAc DA and glycine levels, alcohol intake and the alcohol deprivation effect (ADE) were examined in male Wistar rats following systemic treatment with full or partial GlyT2-inhibitors (Org-25543, Opiranserin and N-arachidonyl-glycine(NAGly)) or a combination of GlyT1 (Bitopertin) and full or partial GlyT2-inhibitors (Org-25543, NAGly), using in vivo microdialysis and a free-choice alcohol consumption model (NAGly only) with repeated cycles of alcohol deprivation. The reduction in alcohol intake following treatment with a partial GlyT2-inhibitor (NAGly, Opiranserin) could be explained by its tendency to slightly elevate basal nAc DA levels, in line with the previously established and more pronounced effects of GlyT1-inhibition. The present findings do not unequivocally support an accumbal, intrasynaptic GlyR-mediated mechanism responsible for alterations in DA output and/or alcohol intake following GlyT2-blockade since at least extracellular glycine levels..."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders

Discovery of a Novel Multitarget Analgesic Through an In Vivo-Guided Approach. (PubMed, Pharmaceuticals (Basel)) - "Compound 29, derived from a novel scaffold inspired by opiranserin and vilazodone pharmacophores, was identified through analog screening in the formalin test. Compound 29 is a promising multitarget analgesic with potent efficacy and favorable pharmacokinetics. Ongoing optimization efforts aim to mitigate side effects and enhance its therapeutic profile for clinical application."

Journal • Preclinical • Neuralgia • Pain

Reduction of postoperative pain and opioid consumption by VVZ-149, first-in-class analgesic molecule: A confirmatory phase 3 trial of laparoscopic colectomy. (PubMed, J Clin Anesth) - P3 | "When compared to placebo, VVZ-149 infusion demonstrated a significant reduction of pain within the first 12 h after surgery with a substantial decrease in opioid use. VVZ-149 rapidly lowers the pain intensity starting at as early as 4 h post-dose, allowing subjects to experience mild pain levels from 8 h through 48 h. Therefore, the analgesic effect of VVZ-149 was shown to effectively relieve pain and reduce opioid use for treating moderate to severe pain in the early postoperative care setting."

Journal • P3 data • Anesthesia • Pain

Phase 3 Efficacy and Safety of VVZ-149 Injections for Postoperative Pain Following Laparoscopic Colectomy (clinicaltrials.gov) - P3 | N=285 | Completed | Sponsor: Vivozon Pharmaceutical Inc.

New P3 trial • Pain

Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery. (PubMed, J Clin Anesth) - P2 | "VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526."

Journal • Anesthesia • CNS Disorders • Depression • Pain • Psychiatry

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Infectious Disease • Novel Coronavirus Disease

Role of VVZ-149, a Novel Analgesic Molecule, in the Affective Component of Pain: Results from an Exploratory Proof-of-Concept Study of Postoperative Pain following Laparoscopic and Robotic-Laparoscopic Gastrectomy. (PubMed, Pain Med) - P2 | "VVZ-149 demonstrated effective analgesia with reduced postoperative pain and opioid requirements. Consistent with the results from the previous Phase 2 study, patients with early rescue requirement had greater benefit from VVZ-149, supporting the hypothesis that VVZ-149 may alleviate the affective component of pain and mitigate excessive use of opioids postoperatively."

Journal • Pain

Non-preserved "Opiranserin Phase 2b Research Result in International Journal" (docdocdoc.co.kr) - P2b, N=60; NCT03997812; Sponsor: Vivozon, Inc.; "Non-Preservation announced on the 15th that the results of a proof-of-concept (PoC) study of the non-narcotic analgesic drug 'opiranserin (VVZ-149)' that it is developing will be published in the international journal Pain Medicine...research team confirmed the analgesic effect of opiranserin in phase 2b, the reduction of narcotic analgesics, and excellent safety and tolerability."

P2b data • CNS Disorders • Pain

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‘Vivozon’s Inist Bio takeover boosts nonnarcotic painkiller trial’ (Korea Biomedical Review) - Lumimicro, an affiliated company with Vivozon, said it would acquire Inist Bio Pharmaceutical and change its company name to Vivozon Healthcare. The acquisition is likely to give Vivizon and Lumimicro the capacity to manufacture the key pipeline, opiranserin (VVZ-149) directly, observers said....Shares of Lumimicro surged 29.87 percent on Wednesday from the previous day and closed at 2,435 won per share. However, on Thursday, the stock price plummeted 27.52 percent to as low as 1,885 won, reflecting investors’ worries over the acquisition plan."

M&A • Stock price • CNS Disorders • Pain

[SEN] Lumi Micro acquires Inist Bio Pharmaceuticals… Securing a production base for 'Opiranserin [Google translation] (Sedaily) - "Non-preservation of a new drug development bio company specializing in pain and central nervous system disease on the 23rd Lumi Micro (082800) It announced that it has acquired Inist Bio Pharmaceuticals....'Through this acquisition of Inist Bio Pharmaceuticals, Non-Conservation and Lumi Micro will lay the foundation for a global comprehensive pharmaceutical group that can range from new drug development to finished drug production and sales. It is expected to accelerate the progress of phase 3 clinical trials in Korea for the non-conservative, innovative new drug Offirangerin (VVZ-149).'"

M&A • Pain

Non-preservation, transfer agreement of Opirangerine injection license to subsidiary Lumi Micro [Google translation] (Maekyung Media Group) - "Bibozon...announced on the 3rd that it has signed an exclusive license agreement in Korea for the non-narcotic anti-drug drug Opirangerine injection with Lumi Micro....With the signing of this license agreement, Bi-Preservation and Lumi Micro plan to quickly promote phase 3 clinical trials in Korea. In addition, non-preservation plans to promote the exclusive production of domestic drug substance and finished drug product of Opirangerine through Lumi Micro, and ultimately secure supply rights to the world."

Licensing / partnership • CNS Disorders • Pain