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celecoxib + tramadol HCl (MR308 / Velyntra / Seglentis)

✓ Approved

Kowa · OPRM1 · Small Molecule

What is celecoxib + tramadol HCl?

celecoxib + tramadol HCl is a small molecule developed by Kowa. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesMR308, Velyntra, Seglentis
CompanyKowa
Drug ClassSmall Molecule
Molecular TargetOPRM1, PTGS2, SLC6A2, SLC6A4
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Kowa

Mechanism of Action

Molecular Targets

celecoxib + tramadol HCl acts on 4 molecular targets:

OPRM1opioid receptor mu 1 (MOP, M-OR-1)
PTGS2prostaglandin-endoperoxide synthase 2 (PHS-2, PGG/HS)
SLC6A2solute carrier family 6 member 2 (NAT1, NET)
SLC6A4solute carrier family 6 member 4 (SERT1, 5-HTTLPR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

celecoxib + tramadol HCl is developed for 2 unique indications across 2 therapeutic areas.

Therapeutic AreaConditionPhase
Gastrointestinal disordersAbdominal pain✓ Approved
Injury, poisoning and procedural complicationsProcedural painPhase III

Related Research Articles

PubMedPharmacological research2026-07-25

Downregulation of COX-2 expression in liver sinusoidal endothelial cell prevented the formation of liver sinusoidal microthrombi through the AKT/mTOR/TSP-1 axis.

Qian Shuaijie S, Gan Can C, Zhao Chong C, Dai Wenting W et al.

Liver sinusoidal microthrombosis (LST) is recognized as an initiating event in fibrogenesis and portal hypertension in chronic liver diseases. Liver sinusoidal endothelial cell (LSEC)-derived chemoattractants recruit neutrophils and macrophages, promoting LST in congestive hepatopathy (CH). However, the driving molecules from LSECs for LST remain unclear. This study aims to elucidate that LSECs inflammatory via cyclooxygenase-2 (COX-2) upregulation triggers metabolic reprogramming promoting thrombospondin-1 (TSP-1)-mediated LST and portal hypertension. A murine model of LST and portal hypertension was established by partial inferior vena cava ligation (pIVCL). LST and portal hypertension were suppressed in both LSEC-specific COX-2 knockout mice (Ptgs2ΔLSEC) and celecoxib-treated wild-type mice induced by pIVCL. RNA sequencing of mouse liver tissue and untargeted metabolomics of human hepatic sinusoidal endothelial cells (HHSECs) revealed that COX-2 inhibition was concurrent with downregulation of the AKT/mTOR pathway, reduced lactate, and decreased TSP-1. In vitro, COX-2-derived prostaglandin E2 (PGE2) activated the AKT/mTOR pathway, driving glycolytic reprogramming and lactate production. In turn, the accumulation of lactate induced by COX-2 upregulation enhanced histone H3K9 lactylation, which transcriptionally upregulated Thbs1 (encoding TSP-1), thereby instigating a prothrombotic phenotype in LSECs. Collectively, this study uncovers a novel pathogenic axis in LST formation, where COX-2 drives a prothrombotic switch in LSECs via AKT/mTOR-mediated metabolic reprogramming and lactate-dependent epigenetic upregulation of TSP-1. Targeting LSEC COX-2 may represent a promising therapeutic strategy for mitigating LST and portal hypertension.

PMID 42498146
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PubMedSurgical endoscopy2026-07-25

Opioid-sparing multimodal pain regimen in combination with intraoperative transversus abdominis plane block reduces opioid use after laparoscopic paraesophageal hernia repair.

Lipson Sophie S, Cassata Nicolas N, Pindicura Sundarachalam S, Chronowski Joseph J et al.

This study evaluated whether a perioperative opioid-sparing multimodal pain regimen with intraoperative transversus abdominis plane (TAP) block reduces opioid use after laparoscopic paraesophageal hernia (PEH) repair while maintaining pain control. A retrospective chart review identified patients who underwent laparoscopic PEH repair at our institution from January 2010 to April 2025. Patients were grouped before and after implementation of a multimodal regimen with TAP block (July 2017). The regimen included scheduled acetaminophen and celecoxib. Outcomes included inpatient and follow-up pain scores (0-10), inpatient morphine milligram equivalents (MME), and opioid prescriptions at discharge or within 30 days. Statistical analysis included chi-squared, t tests, nonparametric tests, and multivariate analysis. A total of 2539 patients were included (813 pre-regimen, 1726 post-regimen). Inpatient opioid use decreased from 86% to 67.6% (p < 0.001), and inpatient oral MME was significantly lower post-regimen (p < 0.001). Opioid prescriptions at discharge declined from 94.7% to 20.6% (p < 0.001). Median inpatient and follow-up pain scores were lower in the multimodal group (p < 0.0001 and p = 0.015). After adjusting for demographics, maximum inpatient pain score, and additional procedures at time of surgery, the post-regimen group remained associated with reduced inpatient opioid use (OR 0.36, p < 0.001). Median length of stay decreased from 2 to 1 day (p < 0.001). 30-day ED visits and readmissions were not significantly different (p = 0.116 and p = 0.404). Implementation of a multimodal opioid-sparing regimen with intraoperative TAP block reduced inpatient and post-discharge opioid use after laparoscopic PEH repair, with lower pain scores and shorter hospital stays without increased ED visits or readmissions.

PMID 42498863
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PubMedTurkish journal of medical sciences2026-07-25

Comparison of ultrasound-guided serratus posterior superior intercostal plane block and thoracic paravertebral block for postoperative analgesia after breast surgery: a prospective randomized noninferiority trial.

Kotanoğlu Mustafa Sırrı MS, Zengin Musa M, Küçük Onur O, Sezgi Atakan A et al.

This noninferiority trial aimed to evaluate whether the serratus posterior superior intercostal plane block (SPSIPB) provides noninferior postoperative analgesia compared with the thoracic paravertebral block (TPVB) after unilateral mastectomy. This prospective, randomized, assessor-blinded, parallel-group noninferiority trial enrolled 60 female patients scheduled for elective unilateral mastectomy. Patients received either ultrasound-guided SPSIPB (n = 30) or TPVB (n = 30) with 30 mL of 0.25% bupivacaine before induction. The primary outcome was visual analogue scale (VAS) pain scores (0-100 mm) at rest and during coughing over 24 h. Noninferiority was assessed using the Hodges-Lehmann median difference with 95% confidence intervals (CIs) and a prespecified margin of 13 mm, corresponding to the validated minimal clinically important difference (MCID). Secondary outcomes included opioid consumption, area under the curve (AUC) for cumulative pain burden, and patient satisfaction. All 60 patients completed the study. At the first postoperative hour, TPVB provided lower VAS scores at rest (median 10.0 vs. 23.0 mm, 95% CI of difference: 0 to 19). For resting VAS, noninferiority was demonstrated at 0 h, 4 h, and 24 h (upper bounds: 11.5 mm, 12.5 mm, and 5.0 mm). The 24-h AUC for resting VAS was comparable between groups (426 mm/h vs. 426.5 mm/h, p = 0.652). SPSIPB produced significantly lower tramadol consumption in the 12-to-24-h interval (median 0 vs. 50 mg, p < 0.001). However, total opioid consumption over the 24 h was comparable (p = 0.070). No block-related complications occurred in either group. Noninferiority of SPSIPB to TPVB was demonstrated for resting pain scores at the majority of postoperative time points after unilateral mastectomy. TPVB provided a transient early-phase analgesic advantage at 1 h and 2 h, while SPSIPB was associated with late-phase opioid sparing. The comparable cumulative pain burden across 24 h suggests that SPSIPB may serve as a periparavertebral alternative to TPVB when sustained analgesia and opioid reduction are clinical priorities.

PMID 42499438
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PubMedJournal of environmental sciences (China)2026-07-25

Humidity-dependent viscosity and hygroscopicity after aging with SO2 of biomass burning single nanoparticle.

Yang Bo B, Xie Zhibo Z, Gui Huaqiao H, Zhang Douguo D et al.

Although understanding the physicochemical properties of nanoparticles is essential to studying their impact on climate and health, information on the viscosity of nanoparticles composed of organic and inorganic salts, as well as the aging process with soluble polluting gases is still rare. In this work, based on a high contrast imaging device enabled by the photonic chip, we measured the hygroscopic growth factors (GFs) of nanoparticles of KCl and glucose mixed in different organic and inorganic dry mass ratios (OIRs). In addition, we also proposed a viscosity retrieval method to quantify the viscosity of the nanoparticles at different relative humidities (RHs) according to the Arrhenius mixing rule and Zdanovskii-Stokes-Robinson approach. Moreover, the retrieval viscosities after deliquescence are almost in perfect agreement with the predicted curves from the Aerosol Inorganic-Organic Mixtures Functional groups Activity Coefficients Viscosity model. Furthermore, the hygroscopic GFs of the components other than glucose in the aged mixed-component particles after deliquescence is slightly higher than that of the aged single component KCl. This might be due to the viscosity of the organic components cause a delay in the volatilization of HCl gas and the formation of K2SO4. For instance, the calculated GFs for the aged mixtures with OIRs of 1:3,1:1 and 3:1 are 1.61, 1.62 and 1.66 at 90 % RH, respectively, while the GF of the aged single component KCl is about 1.60. These results are expected to provide theoretical reference for the future field observation of the various physicochemical property of ambient aerosol samples.

PMID 42498383
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PubMedChemMedChem2026-07-24

CD44-Targeted Delivery of Melittin and Celecoxib via Hyaluronic Acid-Coated Polymersomes for Synergistic Anti-Inflammatory Therapy.

Cho Youngheun Y, Kim Junmin J, Moon Jooho J, Nam Soobin S et al.

Activated macrophages are key effector cells in inflammatory diseases, but the therapeutic use of membrane-active agents such as melittin (MEL) is limited by nonspecific cytotoxicity and hemolysis. Here, we developed a hyaluronic acid (HA)-coated MEL-based polymersome (PMHA) for CD44-targeted codelivery of MEL and celecoxib (CXB). MEL was incorporated into the vesicular membrane, whereas CXB was loaded into the hydrophobic domain. PMHA showed a hydrodynamic diameter of 265.5 ± 1.6 nm, a zeta-potential of -21.14 ± 1.1 mV, a CXB encapsulation efficiency of 70.81 ± 4.18%, and a drug loading capacity of 12.87 ± 1.92%. In lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, anti-CD44 antibody blocking reduced Alexa Fluor 647-labeled PMHA uptake by approximately 37.5%, supporting HA-CD44-mediated internalization. PMHA reduced MEL-associated cytotoxicity and hemolytic activity and enabled pH-responsive CXB release. Codelivery of MEL and CXB suppressed cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expression, with combination index (CI) values of 0.48 and 0.67, respectively. These findings support further evaluation of PMHA as a macrophage-targeted anti-inflammatory nanoplatform.

PMID 42493250
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PubMedBrazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]2026-07-24

Upstream endotoxin removal in recombinant protein purification: an optimised pre-cell disruption strategy for reducing endotoxin contamination of inclusion bodies in Escherichia coli.

Hadadian Shahin S, Sepahi Mina M, Abbasi Mohaddeseh Sheikh MS, Komijani Samira S

Endotoxin contamination remains a critical challenge in recombinant protein production using Gram-negative bacteria, particularly for intracellularly expressed, positively charged proteins prone to lipopolysaccharide (LPS) binding. This study introduces an efficient upstream strategy for LPS removal before the cell disruption, aimed at reducing the endotoxin contamination load in the downstream purification process. A recombinant cationic protein (named as 4mer-S3-DP) was expressed in Escherichia coli (E. coli) BL21 (DE3), and biomass was treated with varying concentrations and incubation times of Tris-HCl and EDTA, as defined by a central composite design (CCD) of response surface methodology (RSM). Endotoxin levels in inclusion bodies (IBs) were quantified using a chromogenic Limulus Amebocyte Lysate (LAL) assay, and statistical modelling was performed to optimize treatment conditions. The final quadratic model demonstrated high predictive accuracy, and response surface analysis revealed that both insufficient and excessive treatment conditions could increase endotoxin contamination. Optimal conditions, consisting of 70 mM Tris-HCl for 30 min and 60 mM EDTA for 5 min, achieved a 2.7-log reduction in endotoxin levels (99.8%) without compromising protein integrity, as confirmed by SDS-PAGE analysis. Experimental validation of the optimum criteria predicted by this model showed no significant difference between predicted and observed endotoxin levels of IBs. This upstream intervention as a simple and effective endotoxin removal approach before the cell lysis could be adaptable to other recombinant proteins expressed in Gram-negative bacterial.

PMID 42493718
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