Vioxx Research Today is a free monthly online journal that collates and summarizes the latest research about Vioxx, including details on osteoarthritis, side-effects, trials, stroke, heart attack.

Using the CatWalk method to assess weight-bearing and pain behaviour in walking rats with ankle joint monoarthritis induced by carrageenan: Effects of morphine and rofecoxib.

Möller KA, Berge OG, Hamers FP

AstraZeneca R&D Södertälje, Local Discovery Research Area CNS & Pain Control, SE-151 85 Södertälje, Sweden.

The CatWalk automated quantitative gait analysis technique has been validated as a method to quantify behaviour in rodent models of neuropathic and arthritic pain. Its suitability for pharmacological testing of pain relief has been questioned, however, based on findings using paw soft tissue plantar inflammation as stimulus. In this study, we investigated the effectiveness of morphine and rofecoxib in reducing pain behaviour in monoarthritic rats. The CatWalk was used to assess print area, weight load and duration of stance for each paw, as well as interlimb coordination, before and 3, 5 and 24h after injection of lambda-carrageenan into one ankle joint. The monoarthritic rat showed a reduced print area, weight load and duration of stance for the injected paw at all times tested, and a significant loss of interlimb coordination at 3 and 5h after injection. Both morphine (3.75 and 15mumol/kg s.c.) and rofecoxib (7.5 and 30mumol/kg p.o.) reduced the effects of carrageenan. In conclusion, behavioural effects interpreted as reflecting movement-related pain in monoarthritic rats and pharmacological treatment of the monoarthritis can objectively and efficiently be quantified in detail by the CatWalk method.

Published 18 July 2008 in J Neurosci Methods.
Full-text of this article is available online (may require subscription).

Articles on Vioxx published 8 July 2008:

Can drug removals involving cyclooxygenase-2 inhibitors be avoided? A plea for human pharmacology.   Trends Pharmacol Sci.

Within the past 20 years many cyclooxygenase (COX) inhibitors were removed for unwanted drug effects shortly after entering the drug market (e.g. benoxaprofen and isoxicam), whereas others (e.g. diclofenac and ibuprofen) were not. This has continued with the suspension of the sale of the COX-2 inhibitors rofecoxib, valdecoxib and lumiracoxib, whereas others (e.g. celecoxib and etoricoxib) are still available. All these compounds share the same molecular mode of action but differ considerably in ... [Abstract] [Full-text]

Articles on Vioxx published 4 July 2008:

Synthesis, Biological Evaluation, and Enzyme Docking Simulations of 1,5-Diarylpyrrole-3-Alkoxyethyl Ethers as Selective Cyclooxygenase-2 Inhibitors Endowed with Anti-inflammatory and Antinociceptive Activity.   J Med Chem.

A series of substituted 1,5-diarylpyrrole-3-alkoxyethyl ethers ( 6, 7, and 8) has been synthesized with the aim to assess if in the previously reported 1,5-diarylpyrrole derivatives ( 5) the replacement of the acetic ester moiety with an alkoxyethyl group still led to new, highly selective and potent COX-2 inhibitors. In the in vitro cell culture assay, all the compounds proved to be potent and selective COX-2 inhibitors. In the human whole blood (HWB) assay, compound 8a had a comparable COX-2 ... [Abstract] [Full-text]

Articles on Vioxx published 30 June 2008:

The anti-proliferative potency of celecoxib is not a class effect of coxibs.   Biochem Pharmacol, 76(2): 179-87.

Celecoxib, a COX-2 (cyclooxygenase-2)-selective inhibitor (coxib), is the only NSAID (non-steroidal anti-inflammatory drug) that has been approved for adjuvant treatment of patients with familial adenomatous polyposis. To investigate if the anti-proliferative effect of celecoxib extends to other coxibs, we compared the anti-proliferative potency of all coxibs currently available (celecoxib, rofecoxib, etoricoxib, valdecoxib, lumiracoxib). Additionally, we used methylcelecoxib (DMC), a close ... [Abstract] [Full-text]

Articles on Vioxx published 24 June 2008:

Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke.   Stroke, 39(7): 2037-45.

BACKGROUND AND PURPOSE: There is limited information regarding the cerebrovascular safety of cyclooxygenase 2 inhibitors (coxibs) and noncoxib nonsteroidal antiinflammatory drugs (NSAIDs). We determined whether specific NSAIDs, including coxibs, are associated with risk of stroke. METHODS: Retrospective cohort study among Tennessee Medicaid enrollees aged 50 to 84 years between January 1, 1999 and December 31, 2004. Noninstitutionalized persons with continuous enrollment in Medicaid and no ... [Abstract] [Full-text]

Articles on Vioxx published 23 June 2008:

Prothrombotic effect of Rofecoxib in a murine venous thrombosis model.   Thromb Res.

The potential prothrombotic effect of the cyclooxygenase-2 (COX-2) inhibitor Rofecoxib (Vioxx) was investigated using murine thrombosis models. In a jugular vein thrombosis model (photochemically induced injury) in lean wild-type mice, Rofecoxib treatment for 4 weeks induced a mild prothrombotic tendency, as indicated by a shorter occlusion time as compared to placebo (median of 12 min versus 36 min; p<0.05). Thrombus size was somewhat, but not significantly, enhanced after Rofecoxib ... [Abstract] [Full-text]

Articles on Vioxx published 19 June 2008:

COX inhibitors downregulate PDE4D expression in a clinical model of inflammatory pain.   Clin Pharmacol Ther, 84(1): 39-42.

Tumor necrosis factor-alpha (TNF-alpha) has a central role in inflammation and is modulated by prostaglandin E(2) (PGE(2)) and cyclic adenosine monophosphate (cAMP). Using microarray, quantitative real-time polymerase chain reaction (qRT-PCR), and protein detection techniques, we showed that ketorolac and rofecoxib had no significant effect on TNF-alpha gene expression in oral mucosal biopsies 3 h after surgery. They both, however, downregulated the gene and protein expression of ... [Abstract] [Full-text]

Was the thrombotic risk of rofecoxib predictible from the French Pharmacovigilance Database before 30 September 2004?   Eur J Clin Pharmacol, 64(8): 829-34.

OBJECTIVES: Rofecoxib was withdrawn from the market on 30 September 2004 following the results of a randomized controlled trial. Following this sudden decision, several controversies occurred in the literature to determine whether this adverse drug reaction (ADR) could have been detected earlier. The aim of this study was to investigate whether this kind of signal could have been seen using the French Pharmacovigilance Database before this date of rofecoxib withdrawal. METHODS: Using cases ... [Abstract] [Full-text]

Therapeutic potential of 1-methylnicotinamide against acute gastric lesions induced by stress: role of endogenous prostacyclin and sensory nerves.   J Pharmacol Exp Ther, 326(1): 105-16.

1-Methylnicotinamide (MNA) is one of the major derivatives of nicotinamide, which was recently shown to exhibit antithrombotic and antiinflammatory actions. However, it is not yet known whether MNA affects gastric mucosal defense. The effects of exogenous MNA were studied on gastric secretion and gastric lesions induced in rats by 3.5 h of water immersion and water restraint stress (WRS) or in rats administered 75% ethanol. MNA [6.25-100 mg/kg intragastrically (i.g.)] led to a dose-dependent ... [Abstract] [Full-text]

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