Aspirin versus the non-acetylated salicylates

Abstract

Bitter im Mund, gesund im Korper German proverb (Strauss, 1968) Historically, it was salicylate--as the acid, sodium salt, aldehyde alcohol or glucoside--that found application in the treatment of rheumatic conditions (for review see Rainsford, 1984). These forms were present in plant-derived extracts which were employed from ancient times until the middle of the last century. With the development of organic chemistry in Germany and France at that time came first the purified compounds, then later synthetic methods (chiefly the Kolbe and Lautermann procedure) for the synthesis of salicylic acid. While no clinical trials of the type and standard employed today were then undertaken to establish the efficacy of salicylic acid or its salts (collectively salicylates) in the relief of pain and soft tissue swelling in various rheumatic conditions, the mere fact that salicylates found such wide use and acceptance in the treatment of rheumatic fever, gout and other arthritides in the latter part of the last century is evidence of a kind for their efficacy. Aspirin (acetylsalicylic acid) really only came into popular use through (a) recognition of the need to obtain a drug which was more palatable and less upsetting to the gastrointestinal tract than sodium salicylate, (b) the powerful competitive forces operating at the time, and (c) clever marketing approaches (Rainsford, 1984). Evidence supporting claims for the reduced gastric irritancy of aspirin over salicylate were initially based on a series of cleverly contrived experiments notably featuring a model of epithelial injury in fish tails immersed into acidic solutions of the two drugs (Rainsford, 1984). The biological relevance of this model with respect to mucosal injury in the gastrointestinal tract must be considered remote, let alone the deductive reasoning for the lack of injury from aspirin (Rainsford, 1984). These and other earlier studies were the basis upon which the marketing of aspirin and especially its claims for superiority over salicylate were based. In contrast, it was less than a decade after aspirin was introduced that the first reports of gastric ulceration in dogs appeared (Chistoni and Lapresa, 1909). This was followed in 1912 by reports of 'gastralgia' from aspirin in