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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

PubMedBMC anesthesiology2026-11-11

Comparison of modified thoracoabdominal nerve block via perichondrial approach with serratus intercostal plane block and rectus sheath block combination in laparoscopic cholecystectomy: a randomized controlled trial.

Bebek Meryem Ecem ME, Yağan Özgür Ö, Doğan Güvenç G, Kayır Selçuk S et al.

Patients undergoing laparoscopic cholecystectomy (LC) may experience severe postoperative pain. Peripheral nerve blocks, as a component of multimodal analgesia, are now widely employed in postoperative pain management. This study investigated the effects of modified thoracoabdominal nerve block (M-TAPA) compared with the combination of rectus sheath block (RSB) and serratus intercostal plane block (SIPB) on postoperative NRS scores, tramadol consumption, and dermatomal spread. This randomized, assessor-blinded trial enrolled 72 patients scheduled for LC. One group received bilateral M-TAPA (Group 1, n = 35), while the other received a combination of bilateral RSB and right-sided SIPB (Group 2, n = 37). All peripheral nerve blocks were performed following surgery and prior to emergence from general anesthesia, using 0.25% bupivacaine; RSB was administered as 10 mL per side, M-TAPA as 20 mL per side, and SIPB as 20 mL on the right side. The primary outcome was postoperative tramadol consumption within the first 24 h; NRS scores, rescue analgesia requirement, and dermatomal spread were secondary outcomes. Static NRS (Numeric Rating Scale) scores measured at 0, 1, and 6 h differed significantly between groups (mean difference [Group 2 - Group 1] 1.27 [95% CI 0.54-2.00], 0.69 [0.14-1.24], and 0.56 [0.12-1.00], respectively). Dynamic NRS scores assessed at 0, 12, and 18 h were also found to be statistically significant between groups (mean difference 1.06 [95% CI 0.25-1.87], 0.45 [0.05-0.85], and 0.52 [0.05-0.99], respectively). Total tramadol consumption over the first 24 h, the primary outcome, did not differ significantly between groups (92.6 ± 26.3 mg vs. 103.9 ± 39.3 mg; mean difference 11.3 mg, 95% CI - 4.4 to 26.9; p = 0.108); however, tramadol consumption between 12 and 24 h was significantly higher in Group 2 compared to Group 1 (24.0 ± 11.7 mg vs. 31.7 ± 17.3 mg; mean difference 7.6 mg, 95% CI 0.7 to 14.6; p = 0.030). The number of patients requiring rescue analgesia was also significantly greater in Group 2 than in Group 1 (absolute risk reduction 24.4%, 95% CI 2.5% to 46.3%; p = 0.034). Both M-TAPA and the combination of RSB with SIPB provided effective postoperative analgesia following LC. Under the conditions of this trial, M-TAPA was associated with lower NRS scores and lower opioid requirements than the combination of bilateral RSB and unilateral SIPB. The study was registered at ClinicalTrials.gov, NCT06241794, registered on January 28, 2024.

PMID 43009777
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PubMedFrontiers in physiology2026-11-11

Differential effects of L-alanine, L-glutamine, L-arginine HCl, and glycine on feed intake and hypothalamic appetite-related responses in layer-type chicks.

Ghashghaei Elham E, Mijiyawa Ahmed A, Riaz Muhammad Faisal MF, Wang Minghui M et al.

While the effects of L-alanine, L-glutamine, L-arginine monohydrochloride (L-arginine HCl) and glycine on feed intake (FI) have been studied in chicks, their hypothalamic neuropeptide responses in layers remain unclear. Therefore, four trials were conducted to investigate the central effects of these amino acids on feed intake and hypothalamic neuropeptides in layer chicks. After intracerebroventricular administration, cumulative FI was measured over 2 hours and gene expression levels were determined using RT-PCR. Our results showed that L-alanine (1 µg and 2 µg) decreased FI at 120 minutes post-injection and was associated with decreased neuropeptide Y (NPY) mRNA expression (P < 0.05). L-glutamine (3 µg) increased FI at 60 minutes post-injection (P < 0.05), but had no significant effect on proopiomelanocortin (POMC), NPY, melanocortin receptor 4 (MC4R) or agouti-related peptide (AgRP) (P > 0.05). L-arginine HCl (1 µg) decreased FI at 120 minutes post-injection, while increasing POMC and MC4R expression, and decreasing NPY (P < 0.05). Glycine (3 µg) significantly reduced FI at all measured time intervals (P < 0.05). It had no impact on POMC expression (P > 0.05), but increased MC4R expression (P < 0.05) and reduced NPY expression more than AgRP expression, although neither was significantly decreased (P > 0.05). These results suggest that the effect of individual amino acids on FI and hypothalamic neuropeptide expression in layer chicks depends on the type and dose of amino acid. The present findings provide evidence of the acute central effects of amino acids in layer chicks.

PMID 43010951
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PubMedCancer discovery2026-11-11

Latent Squamous Plasticity Licensed by Chromatin-State Remodeling Dictates Therapeutic Susceptibility in Cholangiocarcinoma.

Yang Chen C, Xu Nuo N, Ji Shuyi S, Cheng Xifu X et al.

Adenosquamous carcinoma (ASC) in intrahepatic cholangiocarcinoma (iCCA) has long been considered rare (~1-2%), yet its occurrence portends lethal disease progression. Here, we identify latent squamous plasticity, a transcriptionally primed yet histology-silent state that is quantifiable by a squamous transition potential (STP) index. Approximately 20-30% of iCCA patients can be classified as STP-high and experience ASC-like dismal outcomes. Mechanistically, FOSL1 acts as a plasticity trigger, driving a temporally ordered squamous program by reshaping the chromatin landscape. Additionally, it cooperates with p63 in an enhancer-dependent manner to dysregulate PTGS2/COX-2 expression. The resulting intratumoral PGE2 accumulation drives neutrophil-mediated FOXP3-negative type 1 regulatory T-cell (Tr1) polarization and predisposes STP-high tumors to immunotherapy resistance. Through a drug-repurposing screen, we identify celecoxib as a dual-function agent that counteracts latent squamous plasticity while fostering an immune-permissive state, providing a clinically actionable strategy for squamous-biased iCCA now being evaluated in a phase Ib/II trial (NCT07632235).

PMID 43012674
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PubMedRSC advances2026-11-11

An ultra-sensitive and sustainable spectrofluorimetric approach for trace analysis of dinitolmide residues in complex food matrices.

Magdy Galal G, Ebrahim Shaimaa S, El-Domany Ramadan A RA, Belal Fathalla F

The extensive veterinary use of dinitolmide (DNT) as an anticoccidial drug has raised increasing concerns regarding its residual occurrence in poultry-derived foods and the associated risks to consumer health, necessitating the development of rapid, sensitive, and environmentally sustainable analytical methods. Herein, the first spectrofluorimetric method for the determination of DNT residues in poultry matrices is presented. The assay is based on the fluorescence response observed after treatment of DNT with a Zn/HCl system. This response is consistent with the proposed reduction of DNT nitro group(s) to amino group(s), although the structure of the resulting fluorescent product was not independently confirmed. The Zn/HCl-treated product exhibited intense fluorescence emission at 427 nm following excitation at 305 nm, enabling sensitive quantification of DNT. Under the optimized experimental conditions, the method displayed excellent linearity over the concentration range of 30.0-250.0 ng mL-1 (r = 0.9997), with limits of detection and quantification of 7.14 and 21.65 ng mL-1, respectively. The analytical performance was comprehensively optimized by investigating the variables influencing the reduction reaction and fluorescence response, while the fluorescence quantum yield of the formed derivative was also determined. The method was successfully validated and applied to spiked chicken meat, liver, kidney, fat, and skin samples, yielding satisfactory recoveries across the investigated concentration levels. The selected spiking levels were evaluated in relation to the reported maximum residue limits (MRLs) for DNT in the corresponding poultry tissues. Furthermore, the environmental sustainability of the proposed assay was comprehensively assessed using the Multi-color Assessment (MA) Tool, the Analytical Green Star Area (AGSA), the Green Analytical Procedure Index (GAPI), and Analytical GREEnness (AGREE) metric, all demonstrating excellent green analytical performance. Combining operational simplicity, favorable analytical sensitivity, and satisfactory accuracy and precision, the proposed method offers an accessible alternative for determining DNT residues in poultry-derived food products. Although the results support its potential applicability to the investigated poultry matrices, further studies are warranted to strengthen its suitability for routine residue monitoring.

PMID 43011892
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PubMedAnalytical chemistry2026-11-11

Machine Learning Prediction of Molar Mass Distribution of Polymers Forming Fibrous Structures.

Attallah Nashwa L NL, Mobredi Kourosh K, Miranda-Valdez Isaac Y IY, Guccini Valentina V et al.

Molecular weight parameters, such as molar mass distribution (MMD), are core characteristics of polymer materials. While MMD is routinely measured by gel permeation chromatography (GPC), the procedure takes time and resources and requires specific, relatively costly instruments. Polysaccharides such as cellulose and chitin are particularly difficult to dissolve. Herein, we report on the potential of combining hyperspectral imaging (HSI) with machine learning (ML) to predict, at different length scales, the MMDs of these sparingly soluble fibrous polymers from visible-range HS images (420-730 nm) of the solid substrate. A Gaussian process regression model was trained on principal component representations of the HS cubes against MMDs measured by GPC. HCl-vapor hydrolysis served as a controlled degradation pathway that altered the degree of polymerization without detectable morphological change. Although samples appear identical to the eye and under electron microscopy, HSI captures systematic optical differences that can be empirically related to GPC-measured MMD within the investigated hydrolyzed samples. Predicted distributions matched the GPC reference, with curve RMSEs of 0.009-0.027 (native cellulose paper), 0.017-0.050 (cellulose nanopaper), and 0.016-0.029 (chitin nanopaper). The principal features of the bimodal MMD of cellulose nanopaper and the leveling-off degree of polymerization were both recovered. The workflow uses a microscope, a tunable bandpass filter, and a digital camera, completing HSI acquisition and prediction in a few minutes per sample. This approach provides a non-destructive, solvent-free complement to traditional analytical techniques. The presented case study is a proof-of-concept, calibrated against GPC reference data for the specific materials and protocols studied here. Expanding to other polymer systems would require establishing a similar chromatographic reference for each new system.

PMID 43010517
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PubMedRSC advances2026-11-10

Construction of K3PW12O40/ZnIn2S4 heterostructures with a likely direct Z-scheme pathway for enhanced visible-light photocatalytic hydrogen evolution and antibiotic degradation.

Chen Yong Y, Wen Xiaowei X, Yu Chunhong C, Lu Dawei D et al.

Developing efficient visible-light-responsive photocatalysts for solar fuel production and pollutant remediation remains challenging because of insufficient light harvesting and rapid recombination of photogenerated charge carriers. Herein, K3PW12O40/ZnIn2S4 (KPW/ZIS) heterostructured composites were prepared via a facile solvothermal route and evaluated for visible-light-driven H2 evolution and tetracycline hydrochloride (TC-HCl) degradation. Structural and spectroscopic characterizations confirmed the integration of KPW with flower-like ZIS and the formation of intimate interfacial contact between the two components. The incorporation of ZIS broadened the visible-light response of KPW and promoted the separation and interfacial transfer of photogenerated charge carriers. Among the prepared composites, ZK-3 exhibited the highest photocatalytic activity, achieving an H2 evolution rate of 325.61 ± 5.22 µmol g-1 h-1 and a TC-HCl removal efficiency of 69.88 ± 0.91% within 120 min. The corresponding apparent pseudo-first-order rate constant for TC-HCl degradation was 0.010 min-1. Photoelectrochemical measurements, band-structure analysis, reactive-species trapping experiments, and electron spin resonance measurements collectively supported a possible direct Z-scheme charge-transfer pathway. In addition, ZK-3 retained its photocatalytic activity during repeated cycling tests. These results provide a viable approach to constructing polyoxometalate-based sulfide heterostructures for bifunctional solar-energy conversion and environmental remediation.

PMID 43005941
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