Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphodiesterase-4 isoenzymes have absolute specificity for cyclic adenosine-3',5'-monophosphate and are considered potential therapeutic targets for the treatment of chronic inflammatory disorders, such as chronic obstructive pulmonary disease, with small-molecule inhibitors. Several selective phosphodiesterase-4 inhibitors are in clinical trials of chronic obstructive pulmonary disease, including cilomilast and roflumilast. Despite some encouraging data from phase III clinical trials, the current generation of phosphodiesterase-4 inhibitors is hampered by a low therapeutic ratio. Indeed, a major obstacle is their propensity to evoke non-steroid-like side effects, of which nausea, diarrhea, abdominal pain, vomiting, and dyspepsia are the most common. In addition, a particularly worrying potential toxicity of phosphodiesterase-4 inhibitors, also shared by phosphodiesterase-3 inhibitors and other vasodilators, is arteritis/periarteritis. One potential means of improving the therapeutic ratio and safety of phosphodiesterase-4 inhibitors may lie in the development of compounds that have broader phosphodiesterase specificity. Of the 11 phosphodiesterase families that have been unequivocally identified, dual-specificity compounds that inhibit phosphodiesterase-4 and phosphodiesterase-1, phosphodiesterase-3, or phosphodiesterase-7 may offer the best opportunities to enhance clinical efficacy.
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PMID:Phosphodiesterase-4: selective and dual-specificity inhibitors for the therapy of chronic obstructive pulmonary disease. 1626 57

Crohn's disease and ulcerative colitis (UC) are common, chronic inflammatory bowel diseases (IBDs) characterized by episodes of life-altering symptoms such as diarrhea, bleeding, fecal urgency and incontinence, abdominal pain and cramps, and fever lasting weeks to months at a time. Existing treatments are 5-aminosalicyclates or immunosuppressants, but long-term control of IBD is a major problem for a large number of patients. Phosphodiesterase 4 (PDE4) is a key enzyme in cell homeostasis and inflammation and its inhibition has been useful in diseases such as asthma and chronic obstructive pulmonary disease, rheumatoid arthritis and multiple sclerosis. This review focuses on the role of oxidative stress in IBD and the PDE4 inhibitor OPC-6535 (tetomilast), an investigational agent for the treatment of UC. The authors detail the clinical development of the compound and report and provide insight into some of the unpublished data from the recently completed multicenter Phase III trials in UC.
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PMID:Phosphodiesterase 4 inhibitors and inflammatory bowel disease: emerging therapies in inflammatory bowel disease. 1771 33