Nimesulide is a Selective COX-2 Inhibitory, Atypical Non-Steroidal Anti-Inflammatory Drug

Süleyman, Halis; Çadırcı, Elif; Albayrak, Abdulmecit; Halıcı, Zekai

doi:10.2174/092986708783497247

Cited by 90 publications

(73 citation statements)

References 50 publications

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“…We next determined the effects of other coxibs including nimesulide, NS398, and DuP697 (6,29,30) on the sensitivity of purified ovCOX-1 to inhibition by aspirin and by two other nsNSAIDs-indomethacin (INDO) and ibuprofen. INDO is a time-dependent COX inhibitor, whereas ibuprofen is a freely reversible, competitive inhibitor (22).…”

Section: Resultsmentioning

confidence: 99%

Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

Rimon

Sidhu

Lauver

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

167

210

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Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A 2 formed by platelets from AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas COX-2 activity is preferentially blocked by COX-2 inhibitors called coxibs. COXs are homodimers composed of identical subunits, but we have shown that only one subunit is active at a time during catalysis; moreover, many nsNSAIDS bind to a single subunit of a COX dimer to inhibit the COX activity of the entire dimer. Here, we report the surprising observation that celecoxib and other coxibs bind tightly to a subunit of COX-1. Although celecoxib binding to one monomer of COX-1 does not affect the normal catalytic processing of AA by the second, partner subunit, celecoxib does interfere with the inhibition of COX-1 by aspirin in vitro. X-ray crystallographic results obtained with a celecoxib/COX-1 complex show how celecoxib can bind to one of the two available COX sites of the COX-1 dimer. Finally, we find that administration of celecoxib to dogs interferes with the ability of a low dose of aspirin to inhibit AA-induced ex vivo platelet aggregation. COX-2 inhibitors such as celecoxib are widely used for pain relief. Because coxibs exhibit cardiovascular side effects, they are often prescribed in combination with low-dose aspirin to prevent thrombosis. Our studies predict that the cardioprotective effect of low-dose aspirin on COX-1 may be blunted when taken with coxibs.arachidonic acid | adrenic acid | nonsteroidal antiinflammatory drugs | platelet | prostaglandin

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Section: Resultsmentioning

confidence: 99%

Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1

Rimon

Sidhu

Lauver

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

167

210

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“…To support this opinion, COX-2 is responsible for indomethacin's anti-inflammatory effects and COX-1 is responsible for indomethacin's GIS-adverse effects [9]. However, while a less COX-2 selective drug, nimesulide has a protective effect in indomethacin induced gastric ulcer; more COX-2 selective drugs such as celecoxib and rofecoxib does not have a gastroprotective effect [29]. This shows that indomethacin's ulcerative effects on GIS are not explained by a single COX inhibition.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

Albayrak¹,

Hakan²,

Süleyman³

2015

EAJM

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Objective: Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. Materials and Methods:The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Results:Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group. Conclusion:It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its antiulcer effect mechanisms.

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“…Risks and benefits must be individually weighed, and the lowest effective dose should be used for the shortest possible time. Many data suggest that nimesulide shows a low overall risk of cardiovascular events such as myocardial infarction or congestive heart failure 79,80 .…”

Section: Cardiovascular Safetymentioning

confidence: 99%