New French compound bolsters NSAID benefits, suppresses adverse side effects?

Clinicians may have at their disposal a new type of medication that effectively relieves pain, but without the troubling gastrointestinal side effects – including peptic ulcers and bleeding – caused by nonsteroidal anti-inflammatory drugs. NicOx, a pharmaceutical company based in France, is in the process of developing anti-inflammatory drugs (NSAIDS) with nitrix oxide.

Both the beneficial and detrimental effects of NSAIDS are linked to the ability of these drugs to block prostaglanding synthesis. So if you accept the COX2 inhibitor theory, then you have to accept that these agents will only block the production of prostaglandins that do good things. The world is not that simple.

Researchers led by professor of pharmacology and therapeutics at the University of Calgary, Alberta, and chairman of the Scientific Advisory Board for NicOx, theorize that patients need to inhibit both cyclooxygenase (COX)-1 inhibition, but the NO counteracts the detrimental effects that this inhibition causes in the gastrointestinal tract.

They chose nitric oxide because it is a potent anti-inflammatory agent. It produces many of the same beneficial effects in the gut as prostaglandins do, so it is cytoprotective. For this reason, nitric oxide may actually add to the anti-inflammatory properties of NSAIDs. We don’t have clinical data published yet, but the results look promising from Phase II trials.

The selective COX-2 inhibitors and the NO-NSAIDs are two very different approaches. While NO-NSAID is an additive is a subtractive approach. Investigators have taken away part of the activity of the NSAID in order to reduce toxicity. There’s never been any expectation that this would increase efficacy.

Out with the Old? Researchers have shown that patients who use selective COX-2 inhibitors avoid the adverse gastrointestinal side effects associated with NSAIDs such as aspirin, ibuprofen and naproxen explained by an associate professor of internal medicine at the University of Texas Southwestern Medical Center, Dallas. NSAID reduce arthritis pain and inflammation by inhibiting both COX-1 and COX-2 enzymes that produce prostaglandins. However, NSAIDs cause gastrointestinal problems because they also inhibit the protective effects of the COX-1 enzymes on the stomach. The reason COX-2 inhibitors were created was to develop drugs that do not affect the COX-1 form of the enzyme but do inhibit the COX-2 form, which makes them safe for the stomach.