Cyclooxygenase-inhibiting nitric oxide donators for osteoarthritis.
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.
Wallace
John L
JL
Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, L8N 3Z5, Canada. wallacejohn@mcmaster.ca
Viappiani
Serena
S
Bolla
Manlio
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D009288:Naproxen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy*
D016861:Cyclooxygenase Inhibitors; D020030:Nitric Oxide Donors; C111751:naproxen-n-butyl nitrate; D009288:Naproxen