Ibuprofen is a non-steroid drug often used to treat arthritis and relieve pain, fever, and swelling. Its development resulted from a search to find a drug more potent (powerful) and better tolerated than aspirin. When ibuprofen was approved for over-the-counter (OTC) use in the United States in May 1984, it was the first new OTC pain relief medication to enter the marketplace in a generation. Prior to ibuprofen's introduction, nonprescription pain relief was mainly provided by aspirin, marketed since 1899, and acetaminophen, introduced in 1955.
Ibuprofen was developed by Boots Laboratories, a British drug manufacturer and retailer. Early in the 1960s researchers at Boots identified carboxylic acid as the agent that gave aspirin its anti-inflammatory (soothing) property. The Boots group investigated other carboxylic acids. When they found one that was twice as strong as aspirin, they synthesized and tested more than 600 compounds created from these acids. The most active of these, propionic acid, was chosen for clinical trial. It proved to be ineffective in treating rheumatoid arthritis. The researchers next turned to other compounds they had synthesized from phenylalkanoic acids, which seemed to offer broader anti-inflammatory features. The most effective and useful of these was ibuprofen, which Boots began to sell in 1964 in the United Kingdom as the prescription medication Brufen.
Motrin, Advil, and Nuprin
In 1974, ibuprofen first appeared in American pharmacies after Boots granted a nonexclusive license to the Upjohn Company, which marketed ibuprofen as the prescription arthritis-relief drug Motrin. A few years later, Boots began selling its own prescription-form ibuprofen, called Rufen, in the United States.
When the United States Food and Drug Administration approved OTC sales of ibuprofen at a lower dose than in prescription form, two major drug companies immediately geared up for major production. The Whitehall Laboratories division of American Home Products came out with Advil. This was soon followed by Nuprin, which was produced by Upjohn and marketed by Bristol-Meyers. Both companies operated under licenses from Boots, which held the worldwide patent for ibuprofen until May 1985. The companies also held exclusive marketing rights until September 1986. After that date, new manufacturers jumped into the lucrative market with products of their own, including Johnson & Johnson with Medipren, Thompson with Ibuprin, and a number of other companies with generic and private-label brands.
Ibuprofen, aspirin, and acetaminophen are chemically different from one another, but all three give effective relief for minor aches and pains. Ibuprofen causes fewer stomach problems than aspirin. It is also more effective for many women in relieving menstrual discomfort. It seems to be more effective for postsurgical dental pain and soft-tissue injuries, but cannot be taken by people with certain conditions, such as an allergy to aspirin.
A report in the May 1995 issue of Medical Sciences Bulletin detailed a new medical application for ibuprofen. Research has revealed that high doses of ibuprofen slow lung disease in patients with cystic fibrosis. At high doses the drug inhibits release of lysosomal enzymes and the migration, adherence, swelling, and aggregation of neutrophils (white blood cells). Researchers believe that ibuprofen may prolong survival among cystic fibrosis patients with mild lung disease.
Ibuprofen is a well-known drug that possesses analgesic (pain-relieving) and antipyretic (fever-reducing) properties. It is particularly known for its use in pain relief from arthritis. Ibuprofen was discovered by Dr. Stewart Adams and his colleagues in the United Kingdom in the 1950s, patented in 1961, and first made available in 1969. It became available in the United States in 1974. Ibuprofen tablets are sold under the trade names Advil and Motrin. The chemical name of ibuprofen is 2-(4-isobutylphenyl)propanoic acid.
Ibuprofen also has anti-inflammatory properties, and it belongs to a class of therapeutic agents known as nonsteroidal anti-inflammatory drugs, or NSAIDs. Like acetylsalicylic acid (aspirin), another NSAID, and acetaminophen, ibuprofen works by inhibiting the activity of a class of enzymes called cyclooxygenases (COX). These enzymes are significant because they catalyze the synthesis of prostaglandins, molecules that have both positive and negative effects in the body. Prostaglandins are, for example, protective against the development of stomach ulcers, but they can also mediate inflammation (as well as the pain response).
One of the most interesting things about human COX enzymes is that there is more than one of them—definitely two, and probably at least three. This is important to our understanding of the therapeutic effects of ibuprofen, aspirin, and acetaminophen. It had long been suspected that there was more than one COX enzyme, but it was not until 1991 that evidence for the existence of two forms, COX-1 and COX-2, materialized. It was then recognized that COX-1 is present at near constant levels in the body under all conditions (that is, it is a constitutive enzyme), whereas the levels of COX-2 could increase in response to inflammatory conditions (i.e., it is an inducible enzyme). This led to the idea that the side effects of ibuprofen and aspirin (including stomach ulcers) probably arose from inhibition of the constitutive COX-1 enzyme, whereas the therapeutic benefits arose from inhibition of the inducible COX-2 enzyme.
Ibuprofen and aspirin both inhibit COX-1 and COX-2, but they do it in different ways. Ibuprofen binds noncovalently to a COX enzyme and thus competes with the enzyme's natural substrate. (This is referred to as reversible
inhibition.) On the other hand, aspirin forms a covalent bond to a serine residue in the enzyme, and this bond cannot be broken. (This is called irreversible inhibition.) Acetaminophen does not interact with either COX-1 or COX-2, but it is now understood that it may interact with a newly identified cyclooxygenase, COX-3. Selective targeting of the COX enzymes is an exciting area of pharmacology, in which the challenge continues to be the development of drugs that interact with specific COX enzymes.
see also Acetylsalicylic Acid; Acetaminophen; Pharmaceutical Chemistry.
Ian S. Haworth
Flower, Rod J. (2003). "The Development of Cox 2 Inhibitors." Nature Reviews Drug Discovery 2(3):179–191.
International Ibuprofen Foundation. "The History of Ibuprofen." Available from <http://www.ibuprofen-foundation.com/history.htm>.
RxList. "Ibuprofen." Available from <http://www.rxlist.com>.
i·bu·pro·fen / ˌībyoōˈprōfən/ • n. a synthetic compound (C13H18O2) used widely as an analgesic and anti-inflammatory drug. Alternative name: 2-(4-isobutylphenyl) propionic acid.