Hydrogen sulfide (H(2)S), as a novel gaseous mediator, plays important roles in mammalian cardiovascular tissues. In the present study, we investigated the cardioprotective effect of S-diclofenac (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester), a novel H(2)S-releasing derivative of diclofenac, in a murine model of doxorubicin-induced cardiomyopath...

PURPOSE This study compared the pharmacokinetic profile, and systemic and local absorption of diclofenac, following dermal patch application and oral administration in Yorkshire-Landrace pigs. PATIENTS AND METHODS Twelve anesthetized, female, Yorkshire-Landrace pigs were randomized to receive either the dermal patch (FLECTOR(®) patch, 10 × 14 cm; Alpharma Pharmaceuticals, a subsidiary of Pfiz...

Cutaneous adverse reactions to benzodiazepines seem to be rare. We report a 61-year-old man with adverse reactions after ingestion of metamizole, diclofenac, and tetrazepam. Skin prick tests with metamizole, diclofenac, and tetrazepam were negative. Patch tests with metamizole, diclofenac, and tetrazepam (all at 5% in aqueous solution) were performed, and were positive for tetrazepam. Oral chal...

Results Diclofenac (30 μM) decreased the amplitude of rapid (IKr) and slow (IKs) delayed rectifier and L-type calcium currents (ICa) without influencing transient outward (Ito) and inward rectifier (IK1) potassium currents. The action potential was slightly lengthened in ventricular muscle but shortened in Purkinje fibres by diclofenac (20 μM). The maximum upstroke velocity (Vmax) was decreased...

Cyclic AMP-activated intestinal Cl- secretion plays an important role in pathogenesis of cholera. This study aimed to investigate the effect of diclofenac on cAMP-activated Cl- secretion, its underlying mechanisms, and possible application in the treatment of cholera. Diclofenac inhibited cAMP-activated Cl- secretion in human intestinal epithelial (T84) cells with IC50 of ∼ 20 µM. The effect re...

PURPOSE The analgesic and opioid-sparing effects of nonsteroidal anti-inflammatory drugs can be beneficial in postoperative populations. Hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac is an injectable formulation of diclofenac solubilized with HPβCD that is administered as a low-volume intravenous bolus. This open-label, single-dose study examined the effects of age and weight on the pharmacok...

A new glutathione adduct (M4) was tentatively identified, likely as 2'-hydroxy-3'-(glutathione-S-yl)-monoclofenac, using liquid chromatography-tandem mass spectrometry analysis of incubations of diclofenac with human liver microsomes. The same conjugate was not detected in incubations with either rat or monkey liver microsomes. Formation of M4 was mediated specifically by CYP2C9 in human liver ...

PURPOSE To compare the clinical efficacy between locally applied diclofenac diethylamine gel, EMLA cream and systemically given diclofenac sodium for the pain relief during extracorporeal shock wave lithotripsy (SWL) using Dornier Delta Compact Lithotripter. MATERIAL AND METHODS One hundred five patients with renal stones were randomly divided in to 3 groups. Group A was given intramuscular d...

Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed to its classical role as COX-inhibitor. Here we show novel COX-independent effects of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell line proliferat...

The widely used drug diclofenac can cause serious heart, liver and kidney injury, which may be related to its ability to cause mitochondrial dysfunction. Using Saccharomyces cerevisiae as a model system, we studied the mechanisms of diclofenac toxicity and the role of mitochondria therein. We found that diclofenac reduced cell growth and viability and increased levels of reactive oxygen species...