05 - 2009

Expert Opin Biol Ther. 2009 May;9(5):649-57.

Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD).

Geusens P. University Hasselt, University Hospital, The Netherlands. piet.geusens@scarlet.be

BACKGROUND: COX-inhibiting nitric oxide donators (CINODs) are a new class of drugs that combine the actions of the parent COX inhibitor with nitric oxide (NO), with the aim of reducing potential toxicity of the parent drug, while maintaining its analgesic and anti-inflammatory effects. AZD3582 (Naproxcinod) is the first in the class of CINODs. OBJECTIVE/METHODS: To review the effects of NO donation, CINODS in general and naproxen in osteoarthritis (OA), based on literature in PubMed. RESULTS: In preclinical and human studies, this drug produced similar analgesic and anti-inflammatory effects to its parent naproxen, with improved gastrointestinal safety in OA patients. The results of recent clinical trials, which were designed to study effects on blood pressure, are expected shortly, after peer-review. CONCLUSIONS: As naproxen is considered the safest COX inhibitor choice from a cardiovascular perspective, AZD3582 has the potential to become a new drug treatment in patients with OA, in whom pain and function are not controlled by the use of analgesics.

Trends Pharmacol Sci. 2009 Mar;30(3):112-7. Epub 2009 Feb 21.

Cyclooxygenase-inhibiting nitric oxide donators for osteoarthritis.

Wallace JL, Viappiani S, Bolla M. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada. wallacejohn@mcmaster.ca

Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly used medications for the treatment of the symptoms of many chronic inflammatory diseases, including osteoarthritis. Unfortunately, the toxicity of NSAIDs substantially limits their long-term use. Some newer NSAIDs, namely selective cyclooxygenase (COX)-2 inhibitors, exhibit greater gastrointestinal safety, and concomitant use of anti-secretory drugs can also reduce NSAID-induced gastropathy. However, NSAIDs also adversely affect the cardiovascular system. A new class of anti-inflammatory drugs, COX-inhibiting nitric oxide donators (CINODs), has been designed to exert similar anti-inflammatory effects as NSAIDs, but with an improved safety profile. CINODs release nitric oxide, providing protective effects in the gastrointestinal tract and attenuating the detrimental effects on blood pressure normally associated with NSAIDs. We provide an outline of the rationale for CINODs and their activity, in addition to an overview of the pre-clinical and clinical profile of the most advanced CINOD, naproxcinod.