Efficacy and Safety of Morniflumate for the Treatment of Symptoms Associated with Soft Tissue Inflammation

Cremonesi, G; Cavalieri, Luca

doi:10.1177/0300060514567212

Cited by 14 publications

(13 citation statements)

References 63 publications

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“…NFA is an anti-inflammatory drug clinically used for the relief of chronic and acute pain (Cremonesi and Cavalieri, 2015). In comparison with other nonsteroidal anti-inflammatory drugs or nonopioid analgesics, it is not associated with side effects, particularly, reactions in children (Sturkenboom et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…This drug and its derivatives are used worldwide clinically for the relief of chronic and acute pain conditions (Vincent et al, 1999; Kang et al, 2008; Cremonesi and Cavalieri, 2015). As a compound with anti-inflammatory, antipyretic, and analgesic therapeutic activity, NFA has been successfully used in clinical trials in adults (Sauvage et al, 1990; Mero et al, 2013) and children (Manach and Ditisheim, 1990; Lantz et al, 1994; Sturkenboom et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid

Maleeva

Peiretti

Zhorov

et al. 2017

Front. Mol. Neurosci.

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Niflumic acid (NFA) is a member of the fenamate class of nonsteroidal anti-inflammatory drugs. This compound and its derivatives are used worldwide clinically for the relief of chronic and acute pain. NFA is also a commonly used blocker of voltage-gated chloride channels. Here we present evidence that NFA is an efficient blocker of chloride-permeable glycine receptors (GlyRs) with subunit heterogeneity of action. Using the whole-cell configuration of patch-clamp recordings and molecular modeling, we analyzed the action of NFA on homomeric α1ΔIns, α2B, α3L, and heteromeric α1β and α2β GlyRs expressed in CHO cells. NFA inhibited glycine-induced currents in a voltage-dependent manner and its blocking potency in α2 and α3 GlyRs was higher than that in α1 GlyR. The Woodhull analysis suggests that NFA blocks α1 and α2 GlyRs at the fractional electrical distances of 0.16 and 0.65 from the external membrane surface, respectively. Thus, NFA binding site in α1 GlyR is closer to the external part of the membrane, while in α2 GlyR it is significantly deeper in the pore. Mutation G254A at the cytoplasmic part of the α1 GlyR pore-lining TM2 helix (level 2′) increased the NFA blocking potency, while incorporation of the β subunit did not have a significant effect. The Hill plot analysis suggests that α1 and α2 GlyRs are preferably blocked by two and one NFA molecules, respectively. Molecular modeling using Monte Carlo energy minimizations provides the structural rationale for the experimental data and proposes more than one interaction site along the pore where NFA can suppress the ion permeation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid

Maleeva

Peiretti

Zhorov

et al. 2017

Front. Mol. Neurosci.

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“…Non-steroidal anti-inflammatory drugs (NSAID), such as aspirin, ibuprofen, nimesulide, piroxicam, and ketoprofen are widely recommended by physicians for the management of inflammatory conditions (Cremonesi & Cavalieri, 2015). NSAID inhibit the cyclooxygenase-2 (COX-2), which is responsible for the synthesis of pro-inflammatory prostaglandins (Ricciotti & FitzGerald, 2011).…”

Section: Introductionmentioning

confidence: 99%

Phytochemical-rich medicinal plant extracts suppress bacterial antigens-induced inflammation in human tonsil epithelial cells

Wijesundara

Sekhon-Loodu

Rupasinghe

2017

PeerJ

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BackgroundPharyngitis is an inflammatory condition of the pharynx and associated structures commonly caused by the Group A streptococci (GAS). There is a growing interest in discovering plant-based anti-inflammatory compounds as potential alternatives to conventional drugs. This study evaluated anti-inflammatory activity of phytochemical-rich extracts prepared from 12 herbal plants using human tonsil epithelial cells (HTonEpiC) in vitro.MethodsThe HTonEpiC were induced by a mixture of lipoteichoic acid (LTA) and peptidoglycan (PGN) (10 µg/mL; bacterial antigens) for 4 h and then exposed to ethanol extracts (EE) or aqueous extracts (AE) for 20 h. The secretion of four pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assays (ELISA). Total phenolic and total flavonoid contents of the extracts were determined using spectrophotometric methods.ResultsThe herbal plant extracts (≤5 µg/mL) were not cytotoxic to HTonEpiC. The extracts exhibited a broad range of reduction (1.2%–92.6%) of secretion of interleukin-8 (IL-8), human beta defensin-2 (hBD-2), epithelial-derived neutrophil activating protein-78 (ENA-78), and granulocyte chemotactic protein-2 (GCP-2). Both EE and AE of clove, ginger, and echinacea flower and EE from danshen root significantly inhibited the pro-inflammatory cytokine production as induced by LTA and PGN in HTonEpiCs at the concentrations of 1 and 5 µg/mL.DiscussionOur observations indicate that danshen root, clove, ginger, and echinacea flower extracts exhibit an anti-inflammatory effect in HTonEpiCs. The most efficacious extracts from danshen root, clove, ginger and echinacea flowers have potential to be used as natural sources for developing phytotherapeutic products in the management of painful inflammation due to streptococcal pharyngitis.

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“…This drug and its derivatives are widely used in clinics for the relief of chronic and acute pain conditions [56]. Niflumic acid is also known as an inhibitor of several anion channels, including Ca ++ -activated [57-59] and swelling-activated [12] Cl - channels, and was reported to variably affect different membrane ion transport systems, such as anion exchangers [28, 60], the glycine [61], GABA(A) [62] and N-methyl-D-aspartate [63] receptors and T-type calcium channels [64].…”

Section: Discussionmentioning

confidence: 99%

A Potassium-Selective Current Affected by Micromolar Concentrations of Anion Transport Inhibitors

Costa

Civello

Bernardinelli

et al. 2018

Cell Physiol Biochem

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Background/Aims: In the human genome, more than 400 genes encode ion channels, which are ubiquitously expressed and often coexist and participate in almost all physiological processes. Therefore, ion channel blockers represent fundamental tools in discriminating the contribution of individual channel types to a physiological phenomenon. However, unspecific effects of these compounds may represent a confounding factor. Three commonly used chloride channel inhibitors, i.e. 4,4′-diisothiocyano-2,2′-stilbene-disulfonic acid (DIDS), 5-nitro-2-[(3-phenylpropyl) amino]benzoic acid (NPPB) and the anti-inflammatory drug niflumic acid were tested to identify the lowest concentration effective on Cl^- channels and ineffective on K⁺ channels. Methods: The activity of the above mentioned compounds was tested by whole cell patch-clamp on the swelling-activated Cl^- current ICl,swell and on the endogenous voltage-dependent, outwardly rectifying K⁺ selective current in human kidney cell lines (HEK 293/HEK 293 Phoenix). Results: Micromolar (1-10 µM) concentrations of DIDS and NPPB could not discriminate between the Cl^- and K⁺ selective currents. Specifically, 1 µM DIDS only affected the K⁺ current and 10 µM NPPB equally affected the Cl^- and K⁺ currents. Only relatively high (0.1-1 mM) concentrations of DIDS and prolonged (5 minutes) exposure to 0.1-1 mM NPPB preferentially suppressed the Cl^- current. Niflumic acid preferentially inhibited the Cl^- current, but also significantly affected the K⁺ current. The endogenous voltage-dependent, outwardly rectifying K⁺ selective current in HEK 293/HEK 293 Phoenix cells was shown to arise from the Kv 3.1 channel, which is extensively expressed in brain and is involved in neurological diseases. Conclusion: The results of the present study underscore that sensitivity of a given physiological phenomenon to the Cl^- channel inhibitors NPPB, DIDS and niflumic acid may actually arise from an inhibition of Cl^- channels but can also result from an inhibition of voltage-dependent K⁺ channels, including the Kv 3.1 channel. The use of niflumic acid as anti-inflammatory drug in patients with concomitant Kv 3.1 dysfunction may result contraindicated.

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Efficacy and Safety of Morniflumate for the Treatment of Symptoms Associated with Soft Tissue Inflammation

Cited by 14 publications

References 63 publications

Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid

Voltage-Dependent Inhibition of Glycine Receptor Channels by Niflumic Acid

Phytochemical-rich medicinal plant extracts suppress bacterial antigens-induced inflammation in human tonsil epithelial cells

A Potassium-Selective Current Affected by Micromolar Concentrations of Anion Transport Inhibitors

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