Aspirin: Turn of the Century Miracle Drug

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An early advertisement for Bayer aspirin. (Bayer AG)

But how does aspirin affect the production of prostaglandins? In 1976 researchers discovered a particular enzyme, cyclooxygenase, or COX, that is responsible for producing a number of biological mediators, including prostaglandins. Aspirin was found to bind selectively and irreversibly to this enzyme, providing the drug’s beneficial properties. This characteristic differs from that of other well-known NSAIDs (e.g., ibuprofen), which are reversible inhibitors. Further research indicated that there was not one COX enzyme, but three, and that each played a different role in the human body. While one COX enzyme is responsible for the synthesis of prostaglandins during inflammatory reactions, a second is involved in producing prostaglandins that help protect the stomach mucosa. Aspirin affects both enzymes, providing analgesic effects as described, but at high doses sometimes results in stomach irritation. In an effort to separate the two effects pharmaceutical companies have worked hard to develop selective COX inhibitors, such as Celebrex, Vioxx, and Mobic, that reduce inflammation without damaging stomach mucosa. However, a number of issues have arisen with these products, most notably with Vioxx, which recent studies have shown to increase the risk for heart attacks.

Aspirin represents one of humankind’s oldest pharmaceutical agents and continues to be a mainstay therapy for a variety of indications. Like all drugs, aspirin can be toxic at high doses (greater than 150 milligrams per kilogram body weight), but the benefits of aspirin clearly outweigh the risks. We might consider aspirin a true “wonder drug,” as it has been shown to be useful in the treatment of a variety of conditions beyond fever and pain, including prevention of coronary artery disease, heart attack, and stroke. Recent studies suggest that aspirin may also limit the rate of growth and the occurrence of certain types of cancer, including prostate, colon, pancreatic, and lung cancer. While new drugs will continue to treat these and other diseases, aspirin will always hold a significant place in the history of pharmaceutical agents.

Daniel R. Goldberg is a senior principal scientist in the medicinal chemistry department at Boehringer-Ingelheim Pharmaceuticals in Ridgefield, Connecticut. His main research efforts focus on the discovery of new therapies for autoimmune and cardiovascular diseases. This article has been excerpted from Molecules That Matter, a compilation of essays published by the Frances Young Tang Teaching Museum and Art Gallery at Skidmore College and by CHF.