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Anti-Inflammatory/Analgesic Actions of Aspirin

The disclosure of a causal relationship between inhibition of prostaglandin synthesis and anti-inflammatory/analgesic actions of aspirin was not only a satisfactory explanation for its mode of action but also a stimulus for the mechanism-based drug research. These new compounds should be able to block prostaglandin biosynthesis via COX inhibition and should also be more potent than aspirin to allow lower dosing at increased efficacy and reduced side effects. Indomethacin was the first of these so-called aspirin-like drugs [35] and was already used as a reference compound in the pioneering experiments of John Vane (Figure 1.4). Many others followed too. In 2005, there were more than 20 chemically defined substances on the German market, designed and developed as inhibitors of prostaglandin biosynthesis and approved for clinical use as antipyretic/anti-inflammatory analgesics. There were more than 40 (!) brands containing ibuprofen, 35 containing diclofenac, and 12 containing indomethacin, most of them available in several different galenic preparations. However, there were less than 20 preparations containing aspirin as the only active ingredient. Thus, the invention of aspirin did significantly stimulate basic research for new anti-inflammatory analgesics and still does so as is evident from the detection of ATLs and resolvins. Nevertheless, the use of aspirin has also remarkably increased after the discovery of its prostaglandin-related mode of action (Figure 1.5). Today, ASA in its different commercial preparations is still among the most frequently used antipyretic analgesics for self-medication of headache, flu, and other acute inflammatory/painful states. According to a recent survey in Germany (MONICA registry), salicylates

1899 1918 1945 1980 1995 2005

Year

Figure1.5 From 1899to2005 (projected) turnoverof Bayer aspirin in millions of DM (Deutsche Mark). (*): 1 DM (Deutsche Mark) is equivalent to 0.51 € or 0.67 USD (January 2007) [37].

1899 1918 1945 1980 1995 2005

Year

Figure1.5 From 1899to2005 (projected) turnoverof Bayer aspirin in millions of DM (Deutsche Mark). (*): 1 DM (Deutsche Mark) is equivalent to 0.51 € or 0.67 USD (January 2007) [37].

still keep the key position (70-80%) in OTC drugs for these symptoms [36].

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