Tenidap, a structurally novel drug for the treatment of arthritis: Antiinflammatory and analgesic properties

Moore, Peter F.; Larson, David; Otterness, Ivan G.; Weissman, Albert; Kadin, Saul B.; Sweeney, Francis J.; Eskra, James D.; Nagahisa, Atsushi; Sakakibara, Masahiro; Carty, Thomas J.

doi:10.1007/bf02265116

Cited by 37 publications

(20 citation statements)

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“…Its action is related to the inhibition of cyclooxygenases 1 and 2 [64], as well as lipooxygenase 5 [65], but it is also known to modulate a number of membrane transporters and channels, including the rat kidney Na + /HCO 3 -cotransporter (rkNBC) [66] and the inwardly rectifying K + channel Kir2.3 [67]. Tenidap was shown to efficiently block SLC26A3/ DRA activity in Xenopus oocytes [57] and HEK 293 cells [56], as well as pendrin activity in Xenopus oocytes [50].…”

Section: Discussionmentioning

confidence: 99%

Effect of Known Inhibitors of Ion Transport on Pendrin (SLC26A4) Activity in a Human Kidney Cell Line

Bernardinelli¹,

Costa²,

Nofziger³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Pendrin is a Cl^-/I^-/HCO₃^- exchanger playing a fundamental role in controlling blood pressure and airway function, therefore representing an attractive target for the treatment of hypertensive states and respiratory distresses. A review of the literature regarding the ability of some compounds (namely several known inhibitors of ion transport) to block pendrin activity revealed discordant findings. These incongruous findings may be due, in part, to the concentration of compound and/or the nature of the model system used in the study. Methods: Pendrin activity was evaluated by measuring pendrin-dependent iodide influx following overexpression of the transporter in a human kidney cell line, in the presence of selected test compounds or the respective vehicles. Results: Pendrin activity was significantly hampered by 0.1 mM 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB), niflumic acid and tenidap, but was resistant to 0.1 mM 4, 4′-diisothiocyano-2, 2′-stilbene-disulfonic acid (DIDS), furosemide and probenecid. Conclusions: The results of the present study indicate that clinically effective non-steroidal anti-inflammatory drugs (niflumic acid and tenidap) directly inhibit pendrin activity.

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Section: Discussionmentioning

confidence: 99%

Effect of Known Inhibitors of Ion Transport on Pendrin (SLC26A4) Activity in a Human Kidney Cell Line

Bernardinelli¹,

Costa²,

Nofziger³

et al. 2016

Cell Physiol Biochem

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“…Tenidap ([Z]-5-chloro-2,3 dihydro-3-[hydroxy-2-thienyl methylene]-oxo-1H-indole-1-carboxamide, sodium salt) is a novel antirheumatic drug of the oxindole class (17). This drug has a dual action: inhibition of cyclooxygenases (1 8) and production of proinflammatory cytokines such as IL-1, IL-6, and TNFa, in human cell (19) and synovial membrane (20) explants from patients with rheumatoid arthritis.…”

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confidence: 99%

Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. Suppression of metalloprotease and interleukin‐1 activity

Fernandes

Caron

Martel‐Pelletier

et al. 1997

Arthritis & Rheumatism

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Objective. To study, in vivo, the therapeutic effectiveness of tenidap, an antirheumatic drug, on the progression of lesions in an experimental osteoarthritis (OA) dog model. The action of tenidap on the activity and expression of metalloproteases in cartilage, as well as on the bioactivity of interleukin-1 (IL-1) in synovial fluid, was determined.Methods. The anterior cruciate ligament of the right stifle joint of 20 mongrel dogs was sectioned through a stab wound. Dogs were divided into 3 groups: group I (n = 7) received no treatment, group I1 (n = 6) was treated with oral omeprazole (20 mg/day), and group I11 (n = 7) received oral omeprazole (20 mg/day) and a therapeutic dosage of oral tenidap (3 mg/kg twice daily). Four weeks following surgery, the untreated dogs (group I) were killed, and drug treatments were begun for the other dogs (groups I1 and 111). These dogs received medication for 8 weeks (weeks 4-12) and then were killed. Evaluations were made of the incidence and size of osteophytes as well as of the size and grade of cartilage erosions on both the condyles and plateaus. Histologic examination of the severity of the cartilage lesions and synovial inflammation was also performed. Activity levels of collagenase, stromelysin, and gelatinase as well as collagenase-1, collagenase-3, and stromelysin-1 messenger RNA were determined in the cartilage. The level of IL-1 activity in the synovial fluid was also measured. ____Results. Among the dogs with OA, lesions were more severe at 12 weeks than at 4 weeks. Group 111 (tenidap-treated) dogs had a slightly reduced incidence of osteophytes compared with the group I1 (12-week OA) dogs (71% versus loo%), and the size of the osteophytes was significantly diminished (mean f SEM 1.75 f 0.69 mm versus 4.38 f 0.64 mm). Macroscopically, tenidap decreased the size (condyles 6.00 +-2.18 mm' versus 21.08 f 6.70 mm', plateaus 15.50 f 4.77 mm' versus 35.0 f 3.64 mm') and the grade (condyles 0.57 & 0.20 versus 1.17 -C 0.21, plateaus 1.07 f 0.22 versus 2.00 2 0.25) of the cartilage lesions compared with the 12-week OA dogs. At the histologic level, the severity of cartilage lesions was also decreased in the tenidap-treated dogs versus the 12-week OA dogs, both on the condyles (3.43 +-0.54 versus 5.55 f 0.38) and on the plateaus (3.39 f 0.35 versus 5.54 f 0.60). All 3 OA groups showed a significant and similar level of synovial inflammation. Tenidap markedly decreased collagenase, stromelysin, and gelatinase activity, as well as the level of expression of collagenase-3 in the cartilage. Interestingly, the activity level of IL-1 in synovial fluid was also significantly reduced in the tenidap-treated dogs.Conclusion. Tenidap markedly reduced the severity of OA lesions, indicating the effect of this drug in decreasing the progression of disease. It appears that the drug acts by reducing the activity and/or expression of metalloproteases in cartilage, a process known to play a major role in the pathophysiology of OA lesions. This

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“…Indomethacin 3 and tenidap 4 are indole derivatives found to possess antiinflammatory activity with analgesic and anti-pyretic properties. They inhibit production of ecosanoids by inhibition of cyclo-oxygenase (COX) and thereby reduce edema.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2012

IJPSR

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Gastro-intestinal (GI) toxicity is the common adverse effect which has been associated with most of NSAIDs available in the market. So the search for new therapeutic agents with high margin of safety and freedom from normally associated GI toxic effects has been a priority of pharmacologists and pharmaceutical industries. There are virtually limitless series of structurally novel heterocyclic compounds with a wide range of physical, chemical and biological properties. Literature survey reveals that coupling of two or more biodynamic molecules resulted in the enhanced biological activity. The present work embodied here involves synthesis and evaluation of analgesic and anti-inflammatory activities of some bis (indolyl) methane derivatives.

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Tenidap, a structurally novel drug for the treatment of arthritis: Antiinflammatory and analgesic properties

Cited by 37 publications

References 50 publications

Effect of Known Inhibitors of Ion Transport on Pendrin (SLC26A4) Activity in a Human Kidney Cell Line

Effect of Known Inhibitors of Ion Transport on Pendrin (SLC26A4) Activity in a Human Kidney Cell Line

Effects of tenidap on the progression of osteoarthritic lesions in a canine experimental model. Suppression of metalloprotease and interleukin‐1 activity

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