tolfenamic acid / Generic mfg. - LARVOL DELTA

Non-covalent binding of non-steroidal anti-inflammatory drugs to antibiotics: preparation, characterization, physicochemical properties and study of single crystals of tolfenamic acid-enrofloxacin drug-drug salt and their antibacterial and anti-inflammatory activities. (PubMed, Int J Pharm) - "The in vitro antimicrobial activity and anti-inflammatory activity of TA-ENR were also somewhat improved compared to TA and ENR. The success of this work implies that we may provide new ideas for designing and synthesizing solid drugs with better physicochemical properties and bioactivity, as well as for the treatment of septic arthritis, through the formation of drug-drug co-crystals/salts."

Journal • Immunology • Rheumatology

Pharmacokinetic Characteristics of Tolfenamic Acid in Freshwater Crocodiles (Crocodylus siamensis). (PubMed, Animals (Basel)) - "Good bioavailability levels and favorable plasma concentrations of TA were obtained in freshwater crocodiles after IM administrations, considering that this is the preferred route of drug administration in freshwater crocodiles. Multi-dose and pharmacodynamic studies are needed to better establish the safety and efficacy of using TA in this crocodilian species."

Journal • PK/PD data

Local Antimicrobial Potential of Bupivacaine and Tolfenamic Acid-Loaded Ultra-High Molecular Weight Polyethylene (UHMWPE) for Orthopedic Infection. (PubMed, Bioengineering (Basel)) - "For the dual drug-loaded UHMWPE, the drug release rate from BP/TA combinations was interestingly not a direct function of the loaded drug weight percent, potentially due to the hydrophobicity of TA and the interactions between the two drugs. Combinations of BP and TA at the higher total drug concentration (10 and 20%) showed a prolonged antibacterial effect against S. aureus, with great potential for prophylactic use."

Journal • Infectious Disease • Orthopedics • Pain

Ru(II)-Fenamic-Based Complexes as Promising Human Ovarian Antitumor Agents: DNA Interaction, Cellular Uptake, and Three-Dimensional Spheroid Models. (PubMed, Inorg Chem) - "Cancer resistance to chemotherapeutic agents such as cisplatin presents a significant challenge, leading to treatment failure and poor outcomes...Four Ru(II) complexes with fenamic acid derivatives were synthesized and characterized: [Ru(L)(bipy)(dppp)]PF6, where L represents fenamic acid (HFen, complex 1), mefenamic acid (HMFen, complex 2), tolfenamic acid (HTFen, complex 3), and flufenamic acid (HFFen, complex 4)...These complexes also altered cell morphology, reduced cell density, and inhibited colony formation in the A2780 cells. Staining assays indicated induced cell death and organelle damage, highlighting their potential as promising antitumor agents."

Journal • Oncology • Ovarian Cancer • Solid Tumor

Degradation of fenamates. (PubMed, Profiles Drug Subst Excip Relat Methodol) - "The clinically prescribed drugs of the fenamate group include mefenamic acid, tolfenamic acid, meclofenamic acid, flufenamic acid, and niflumic acid. Studies have been performed to remove these contaminants from water sources by various forced degradation procedures, but the number of studies in this area is limited. In this chapter, an effort has been made to review the degradation of multiple fenamates in different systems and the factors affecting the degradation rates with the proposed degradation pathways."

Journal • Review • Pain

Structural and theoretical studies of amantadinium fenamates. (PubMed, Acta Crystallogr B Struct Sci Cryst Eng Mater) - "Two new crystals of amantadinium salts were obtained from fenamic and tolfenamic acid. The salt of fenamic acid is a model compound for interaction analysis, while amantadinium tolfenamate is a composition of a drug used in the treatment of symptoms of Parkinsonism and as a nonsteroidal anti-inflammatory drug. The crystal structures were studied and a theoretical analysis of the hydrogen bonds and weak interactions was carried out using quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) methods."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Green synthesis, anti-inflammatory evaluation and molecular docking of novel pyridines via one pot multi-component reaction using ultrasonic irradiation. (PubMed, Mol Divers) - "The anti-inflammatory activity of the newly compounds was examined with the reference drug Ibuprofen. Furthermore, the newly compounds were studied in their molecular docking simulations against the enzyme Human Cyclooxygenase-2, with Tolfenamic Acid as a reference ligand (PDB ID: 5IKT). Compound 4b demonstrated a robust binding affinity with the target protein 5ikt, evidenced by its binding affinity score of - 11.16 kcal/mol, which is the highest among the studied compounds."

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Perioperative pain management in dogs and cats: Attitudes and practices among Thai veterinarians. (PubMed, Vet Anaesth Analg) - "This study reveals variations in perioperative pain management practices in dogs and cats among veterinarians, influenced by sex, graduation year, education and workplace."

Journal • Anesthesia • Pain

Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP. (PubMed, ACS Chem Biol) - "Although tolfenamic acid did not block the substrate recognition and linear ubiquitination activity of HOIP, a ligand of the uncharacterized PUB pocket of HOIP (LUPH), by chemical linking pomalidomide with tolfenamic acid, degraded HOIP, reduced NEMO ubiquitination and p65 phosphorylation, and eventually inhibited NF-κB activation and breast cancer cell proliferation. Our work proposes an alternative strategy to target the nonfunctional pocket of the PUB domain with high sequence diversity to promote HOIP degradation, rather than targeting the conserved RBR domain to block the catalytic function of HOIP."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Synthesis, structure and biological activity of silver(I) complexes containing triphenylphosphine and non-steroidal anti-inflammatory drug ligands. (PubMed, J Inorg Biochem) - "The binding properties of tolfenamic acid, ibuprofen and the two complexes with DNA and BSA were investigated using UV or fluorescence spectroscopy. The intracellular reactive oxygen species (ROS) assay showed complex 1 induced the ROS generation in HeLa cells in a concentration dependent manner. Flow cytometry analysis showed complex 1 could suppress the HeLa cells growth during the G0/G1 phase and induce apoptosis in dose-depended manner."

Journal • Oncology

Pharmacokinetics of tolfenamic acid in ducks (Anas platyrhynchos domestica) after different administration routes. (PubMed, Br Poult Sci) - "Tolfenamic acid was absorbed rapidly, eliminated quickly and exhibited a small distribution volume in Pekin ducks. Pharmacokinetic parameters, including maximum concentration, area under the plasma concentration - time curve and bioavailability, were found to be different in ducks from other bird species."

Journal • PK/PD data • Pain

Plasma and Milk Pharmacokinetics and Estimated Milk Withdrawal Time of Tolfenamic Acid in Lactating Sheep. (PubMed, Vet Med Sci) - "A decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians' decision-making processes."

Journal • PK/PD data

Coordination compounds of cobalt(II) with carboxylate non-steroidal anti-inflammatory drugs: structure and biological profile. (PubMed, Dalton Trans) - "Fourteen cobalt(II) complexes with the non-steroidal anti-inflammatory drugs sodium meclofenamate, tolfenamic acid, mefenamic acid, naproxen, sodium diclofenac, and diflunisal were prepared in the presence or absence of a series of nitrogen-donors (namely imidazole, pyridine, 3-aminopyridine, neocuproine, 2,2'-bipyridine, 1,10-phenanthroline and 2,2'-bipyridylamine) as co-ligands and were characterised by spectroscopic and physicochemical techniques. The complexes demonstrated tight and reversible binding to human and bovine serum albumins and the binding site of bovine serum albumin was also examined. In order to assess the antioxidant activity of the compounds, the in vitro scavenging activity towards free radicals, namely 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid), and their ability to reduce H2O2 were studied."

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Photolysis of tolfenamic acid in aqueous and organic solvents: a kinetic study. (PubMed, RSC Adv) - "A total of 17 photoproducts have been identified through LC-MS, of which nine have been reported for the first time. It has been confirmed through electron spin resonance (ESR) spectrometry that the excited singlet state of TA is converted into an excited triplet state through intersystem crossing, which results in an increased rate of photodegradation in acetonitrile."

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Pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid in rainbow trout (Oncorhynchus mykiss). (PubMed, Vet Med Sci) - "While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout."

Journal • PK/PD data • Inflammation • Pain

Docking and molecular dynamic simulations of Mithramycin-A and Tolfenamic acid against Sp1 and survivin. (PubMed, Process Biochem) - "Subsequent molecular dynamics simulations followed the same trend as initial binding energy calculations and showed crucial amino acids involved in each Mithramycin-A-protein complex. Our findings warrant further investigation into Mithramycin-A and its specific interaction with Sp1 and their downstream targets giving a better understanding of Mithramycin-A and its potential as an effective cancer treatment."

Journal • Oncology • BIRC5

Antiseizure properties of fenamate NSAIDs determined in mature human stem-cell derived neuroglial circuits. (PubMed, Front Pharmacol) - "Mefenamic acid, flufenamic acid, meclofenamic acid, niflumic acid, and tolfenamic acid (each tested at 10-100 μM) attenuated 4-aminopyridine (4-AP, 100 μM) evoked epileptiform activity in a dose-dependent fashion. These actions were as effective diazepam (3-30 μM) and up to 200 times more potent than phenobarbital (300-1,000 μM)...The antiseizure actions of fenamates were also not replicated by either of the two non-fenamate NSAIDs, ibuprofen (10-100 μM) or indomethacin (10-100 μM), indicating that inhibition of cyclooxygenases is not the mechanism through which fenamates have anticonvulsant properties. This study therefore shows for the first time, using functionally mature human stem cell-derived neuroglial circuits, that fenamate NSAIDs have powerful antiseizure actions independent of, and in addition to their well-established anti-inflammatory properties, suggesting these drugs may provide a novel insight and new approach to the..."

Journal • CNS Disorders • Epilepsy • Inflammation

Design, Synthesis and Evaluation of Antioxidant and NSAID Derivatives with Antioxidant, Anti-Inflammatory and Plasma Lipid Lowering Effects. (PubMed, Molecules) - "Amides containing methyl esters of γ-aminobutyric acid (GABA), L-proline and L-tyrosine, and esters containing 3-(pyridin-3-yl)propan-1-ol were synthesized by conjugation with 3,5-di-tert-butyl-4-hydroxybenzoic, an NSAID (tolfenamic acid), or 3-phenylacrylic (cinnamic, (E)-3-(3,4-dimethoxyphenyl)acrylic and caffeic) acids...The hypocholesterolemic effect of the compounds was comparable to that of simvastatin, a well-known hypocholesterolemic drug. Additionally, all compounds lowered blood triglycerides. The synthesized compounds with multiple activities, as designed, may be useful as potential candidates for conditions involving inflammation, lipidemic deregulation and oxygen toxicity."

Journal • Dyslipidemia • Inflammation • Metabolic Disorders

Irradiation Behavior of Analgesic and Nonsteroidal Anti-Inflammatory Drug-Loaded UHMWPE for Joint Replacement. (PubMed, Biomacromolecules) - "The incorporation of bupivacaine hydrochloride and tolfenamic acid in UHMWPE resulted in either single- or dual-drug loaded materials that can be sterilized by gamma irradiation. These compositions were found to be promising for the development of clinically relevant drug-eluting implants for joint replacement."

Journal • Orthopedics • Pain

Evaluation of zootechnical parameters of piglets born and suckled from dams treated with a non-steroidal anti-inflammatory drug after farrowing. (PubMed, Open Vet J) - "To evaluate zootechnical parameters of piglets born and suckled from dams treated postpartum with tolfenamic acid (TA) at a commercial farm...The within-litter weaned weight variation in the TA group was not significant (p = 0.11) at 6.50 ± 1.11 kg in the anterior suckling position versus 6.76 ± 1.01 kg in the posterior teat suckling positions, while the difference was significant (p < 0.05) in the control group, at 5.61 ± 0.68 kg versus 5.37 ± 0.75 kg, respectively. Piglets in the TA group had statistically significant improved zootechnical performances, while their within-litter weaned weights did not differ significantly."

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Do metastable polymorphs always grow faster? Measuring and comparing growth kinetics of three polymorphs of tolfenamic acid. (PubMed, Chem Sci) - "Using approximations for describing the volume of TFA crystals, we show that while crystals of the metastable TFA-II grow the fastest at all solution concentrations, crystals of the metastable TFA-IX become kinetically competitive as the driving force for crystallisation increases. Overall, both metastable forms TFA-II and TFA-IX grow faster than the stable TFA-I."

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Tolfenamic Acid Derivatives: A New Class of Transcriptional Modulators with Potential Therapeutic Applications for Alzheimer's Disease and Related Disorders. (PubMed, Int J Mol Sci) - "Specific levels of SP1-driven genes and AD biomarkers such as amyloid precursor protein (APP) and Tau proteins were also decreased as part of this targeted systemic response. These small molecules, therefore, offer a viable alternative to achieving desired therapeutic outcomes by interfering with both amyloid and Tau pathways with limited off-target systemic changes."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Developmental Disorders • APP • SP1

The Influence of Solvent Selection upon the Crystallizability and Nucleation Kinetics of Tolfenamic Acid Form II. (PubMed, Cryst Growth Des) - "The TFA concentration and critical supersaturation at the crystallization onset is found to be directly correlated with TFA/isopropanol solutions having the highest values of solubility and critical supersaturation. Intermolecular modeling of solute-solvent interactions supports the experimental observations of the solubility and crystallizability, highlighting the importance of understanding solvent selection and solution state structure at the molecular level in directing the solubility, solute mass transfer, crystallizability, and nucleation kinetics."

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Tolfenamic acid negatively regulates YAP and TAZ expression in human cancer cells. (PubMed, Biochim Biophys Acta Mol Cell Res) - "Proteins that affect YAP and TAZ regulation, such as NAG-1 and several YAP/TAZ E3 ligases, were not involved in TA-mediated YAP/TAZ degradation. In summary, our results indicate that TA affects phosphodegron sites on YAP/TAZ, demonstrating a novel effect of TA in tumorigenesis."

Journal • Oncology • Targeted Protein Degradation • GDF15 • TAFAZZIN

Exploring the Potential of Fenamate NSAID Analogs for the Treatment of Alzheimer's Disease (AAIC 2023) - "Although the blood-brain barrier (BBB) prevents uptake of most pharmaceuticals, our laboratory previously showed that tolfenamic acid (TA), a fenamate non-steroidal anti-inflammatory drug (NSAID) with known anti-cancer effects, can cross the BBB and slow the progression of AD (Zawia et al, 2018)... We found a set of differentially expressed genes that have been linked to processes involved in AD pathogenesis such as the production and clearance of neurotoxic Aβ peptides, tau phosphorylation, regulation of oxidative stress, and inflammatory processes. These results suggest that the drugs may influence pathways related to the pathogenesis of AD and support the potential of drug repurposing of fenamate NSAIDs such as TA, and its analogs CBA and NA, as a strategy for cancer and neurodegenerative disease therapy. Further research is needed to confirm the effect of the analogs on AD biomarkers and their efficacy as therapeutics for AD."

Alzheimer's Disease • CNS Disorders • Dementia • Oncology