Inhibition of interleukin 1 synthesis by tenidap: A new drug for arthritis

Otterness, Ivan G.; Bliven, Marcia L.; Downs, James T.; Natoli, Edward J.; Hanson, Douglas C.

doi:10.1016/1043-4666(91)90495-y

Cited by 54 publications

(23 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Tenidap may reduce MMP synthesis through several mechanisms. Reduction in IL-1 and/or TNFa synthesis in vivo is possible given reports that tenidap inhibits cytokine synthesis (17,62,63). The marked reduction of the severity of synovial inflammation by the drug is another element supporting this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…Tenidap sodium [(Z)-5-chloro-2,3 dihydro-3-(hydroxy-2-thienyl methy1ene)-Zoxo-1 H-indole-1-carboxamide, sodium salt] is a novel drug which has combined cyclooxygenase-and 5-lipoxygenaseinhibitory activity in vitro (15,16). Several of its properties, such as its ability to modulate cytokine synthesis (17), its in vitro activity in protecting cartilage integrity (18), its potent inhibitory action on the release of activated neutrophil collagenase (19), as well as its antiinflammatory and analgesic activities (20), make it an attractive antirheumatic drug.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Fernandes

Martel‐Pelletier

Otterness

et al. 1995

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. To examine the effects of tenidap and diclofenac on osteoarthritic lesions and metalloprotease activity in experimental osteoarthritis (OA).Methods. The anterior cruciate ligament of the right stifle joint of 25 mongrel dogs was sectioned by a stab wound. Seven dogs received no treatment, 6 were treated with oral omeprazole (20 mg/day), another 6 were treated with diclofenac (0.25 mg/kg/twice daily) plus omeprazole (20 mg/day), and 6 received oral tenidap (3 mg/kg/twice daily) plus omeprazole (20 mg/ day). The dogs received medication for 8 weeks; all dogs were killed at the end of this period. Eight normal dogs were used as controls. Lesions were evaluated macroscopically for the incidence and size of osteophytes and the area and grade of cartilage erosions on the condyles and plateaus, along with histologic evaluation of the severity of the cartilage lesions and synovial inflammation. Stromelysin and collagenase activities and the collagenase messenger RNA (mRNA) level were measured in cartilage and synovial membrane.Results. Compared with the untreated or omeprazole-treated OA groups, the dogs treated with tenidap exhibited significant reduction in the incidence (P 5 0.001) and size (P 5 0.0001) of osteophytes. Tenidap also significantly decreased the size and grade of cartilage macroscopic lesions, as well as the histologic severity of cartilage lesions on both condyles and plateaus. The histologic severity of synovial inflammatory reaction was also significantly reduced (P I 0.003) in the tenidap group. Tenidap markedly decreased stromelysin and collagenase activity in both cartilage (stromelysin P I 0.003; collagenase P I 0.01) and synovial membrane (stromelysin P 5 0.003; collagenase P 5 0.005). Moreover, tenidap also decreased the collagenase mRNA level in cartilage (P 5 0.005) and synovial membrane (P 5 0.002). Diclofenac slightly reduced the incidence and size of osteophytes and cartilage lesions, but these changes were not statistically significant. Diclofenac had no effect on the severity of synovial inflammation, metalloprotease activity, or collagenase expression.Conchsion. This study showed that tenidap had a more potent anti-osteoarthritic effect than diclofenac in this model. The effect of the drug in suppressing metalloprotease synthesis, a process known to play a major role in the pathophysiology of osteoarthritic lesions, may explain its mechanism of action.Transection of the anterior cruciate ligament of the dog knee leads to articular changes which resemble the morphologic and biochemical changes seen in human osteoarthritis (OA) (1-3). Cartilage lesions are probably related to mechanical as well as biochemical factors, including the enzymatic cleavage of matrix macromolecules (4). Matrix metalloproteases (MMP), such as collagenase and stromelysin, have been found to be significantly increased in OA cartilage and synovial membrane, in humans as well as in the experimental dog model (4-6). It is becoming more and more

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Fernandes

Martel‐Pelletier

Otterness

et al. 1995

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

show abstract

“…We reached similar conclusions when studying IL-6 in patients with cardiac myxoma (10). This is of importance since IL-6 production in vivo can at present be only estimated from serum IL-6 levels, which actually reflect a minor portion of the IL-6 produced in vivo, i.e., the portion not absorbed by either cell surface receptors or the kidneys.…”

mentioning

confidence: 62%

Reply

Kushner

1992

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…It has been found to inhibit significantly the production of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor (TNF) in lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes [9] and the production of IL-I in LPS-stimulated murine macrophages [10]. Tenidap has also been found to inhibit cytokine-mediated bone resorption [11] and IL-I stimulated cartilage degradation [12].…”

Section: Co-existing Arthritis and Hypertension Is A Commonmentioning

confidence: 99%

The effect of tenidap on the anti‐hypertensive efficacy of thiazide diuretics in patients treated for mild to moderate hypertension.

Rapeport

Grimwood

Korlipara

et al. 1995

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 This randomised, placebo-controlled, double-blind, parallel-group study was conducted to assess the effect of tenidap sodium 120 mg, a novel anti-arthritic cytokine modulating drug, on the hypotensive efficacy of the thiazide diuretics hydrochlorothiazide or bendrofluazide. 2 Twenty-three male and female patients, aged 41-78 years, with mild to moderate, uncomplicated, essential hypertension controlled with thiazide diuretic therapy, received either a single daily dose of tenidap sodium 120 mg or matched placebo for 22 days in addition to their diuretic therapy. Changes between baseline and endpoint in supine and standing systolic and diastolic pressures and pulse rate were compared between treatment groups. 3 Daily treatment with tenidap reduced the anti-hypertensive efficacy of the thiazide diuretics. Blood pressure tended to increase marginally and the increase in mean standing diastolic pressure observed with tenidap was significantly greater than the change in the placebo group. All pressures tended to decrease in the placebo group and all endpoint measurements were within 7 mm Hg of baseline in both groups. 4 Treatment-related side effects of mild to moderate severity were reported in two subjects receiving tenidap, but in neither case was treatment discontinued. Two subjects receiving placebo also experienced side effects considered to be treatment-related and both were withdrawn from the study. 5 The results of this study suggest that tenidap may be given to patients treated for mild to moderate essential hypertension controlled with thiazide therapy; however, the patient's blood pressure should be regularly monitored.Keywords tenidap sodium hypertension thiazide diuretic hypotension drug interaction arthritis

show abstract

Inhibition of interleukin 1 synthesis by tenidap: A new drug for arthritis

Cited by 54 publications

References 10 publications

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Effects of tenidap on canine experimental osteoarthritis i. morphologic and metalloprotease analysis

Reply

The effect of tenidap on the anti‐hypertensive efficacy of thiazide diuretics in patients treated for mild to moderate hypertension.

Contact Info

Product

Resources

About