Building a better aspirin: gaseous solutions to a century‐old problem

• Published in: British journal of pharmacology 2007-10, Vol.152 (4), p.421-428
• Main Author: Wallace, J L
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; arthritis; Aspirin - adverse effects; Aspirin - chemistry; Aspirin - therapeutic use; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Chemistry, Pharmaceutical - trends; cyclooxygenase; Diseases of the osteoarticular system; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Hemorrhage - chemically induced; Gastrointestinal Hemorrhage - prevention & control; Humans; Hydrogen Sulfide - metabolism; hydrogen sulphide; inflammation; inflammatory bowel disease; Medical sciences; Miscellaneous. Osteoarticular involvement in other diseases; Models, Biological; Molecular Structure; nitric oxide; nonsteroidal anti‐inflammatory drugs; Other diseases. Semiology; pain; Pharmacology. Drug treatments; prostaglandin; Reviews; Stomach Ulcer - chemically induced; Stomach Ulcer - prevention & control; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707396

The gastrointestinal adverse effects of nonsteroidal anti‐inflammatory drugs (NSAIDs) have been recognized since shortly after the introduction of aspirin to the marketplace over a century ago. However, the underlying pathogenesis of NSAID‐induced gastropathy remains incompletely understood. Advances in understanding some of the factors that contribute to the mucosal injury have provided clues for the development of safer NSAIDs. The inhibitory effects of nitric oxide (NO) on NSAID‐induced leukocyte adherence were exploited in the development of NO‐releasing NSAIDs. As well as eliciting less gastrointestinal damage than conventional NSAIDs, these drugs do not elevate blood pressure and show anti‐inflammatory effects, additional to those of the parent drugs. Modification of other drugs in a similar manner (i.e., NO‐releasing derivatives) has similarly resulted in more effective drugs. More recently, hydrogen sulphide‐releasing derivatives of NSAIDs and of other drugs, have been developed, based on the observed ability of H2S to reduce inflammation and pain in experimental models. H2S‐releasing NSAIDs produce negligible gastric damage and exhibit enhanced anti‐inflammatory potency as compared to the parent drugs. The NO‐NSAIDs and H2S‐releasing NSAIDs represent examples of new anti‐inflammatory drugs with greatly reduced toxicity and improved therapeutic activity, both created through the concept of exploiting the beneficial effects of endogenous gaseous mediators. British Journal of Pharmacology (2007) 152, 421–428; doi:10.1038/sj.bjp.0707396; published online 16 July 2007