Biochemical pharmacology of nonsteroidal anti-inflammatory drugs.
Aspirin and conventional nonsteroidal anti-inflammatory drugs are nonselective inhibitors of cyclooxygenase-1 (COX-1) and COX-2 enzymes. Two classes of selective COX-2 inhibitors: (1) sulfonamides, such as L-745,337, and (2) tricyclic methyl sulfone derivatives, such as SC58125, have been developed. X-ray crystal structures of COX-1 and COX-2 have provided valuable information regarding the structural basis for their COX-2 selectivity. These compounds have less gastrointestinal complications in animal experiments. Their clinical efficacy and side-effects are being evaluated. Salicylate has very weak activity against either COX isoform and yet possesses anti-inflammatory actions. Recent studies indicate that it suppresses the expression of genes involved in inflammation. These activities may provide a plausible explanation for the pharmacological dilemma and, furthermore, may represent novel mechanisms for controlling inflammation.
Wu
K K
KK
Vascular Biology Research Center and Division of Hematology, University of Texas-Houston Medical Center, 77030, USA. kkwu@heart.med.uth.tmc.edu
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012459:Salicylates; D020156:Salicylic Acid