COX-2 Inhibitor Drugs
COX-2 drugs are used as pain relievers. This page describes the history of the development of pain reliever drugs and the recent development of drugs that inhibit the COX-2 enzymes, such as Vioxx and other COX-2 drugs.
The medicinal use of substances to reduce pain has been common for over 5000 years. In Egypt and Greece, tree bark, dried leaves and other substances were used to relieve the pain of childbirth and to reduce fever. The first major pain relieving drug, aspirin (acetylsalicylic acid), was developed in 1875 by the Bayer Company. Aspirin became recognized and widely used as the primary drug for reducing pain and inflammation, but an understanding of how aspirin worked was yet to come for almost 100 years.
An Understanding of Prostaglandins
It was not until the 1960s that it was discovered that aspirin inhibited the production of prostaglandins. Prostaglandins are produced in large quantities throughout the body during pain, fever, inflammation and swelling. In the 1970s, researchers learned that Aspirin blocked the prostaglandins via an enzyme called cyclooxygenase (COX), which led to the production of the prostaglandins. It was by blocking the production of COX enzymes that aspirin was able to stop the production of prostaglandins.
Once the mechanism of blocking prostaglandins was understood, a broad range of COX-inhibiting drugs was developed for pain relief. These medications, referred to as NSAIDs (non-steroidal anti-inflammatory drugs), became widely used for acute and chronic pain associated with diseases such as arthritis, colic, dysmenorrhea (menstrual pain), fever and swelling. These COX inhibitors reduce the symptoms of inflammation without eliminating the underlying cause of the disease. They do not provide protection for the tissues or joints affected by the inflammation. NSAIDs include drugs such as Tylenol and ibuprofen (Motrin, Advil). It is estimated that over 30 million patients worldwide consume NSAIDs daily. Of the 30 million, 40% are over the age of 60.
Two Types of COX Enzymes
In the 1990s, it was discovered that two different kinds of COX enzymes existed: COX-1 and COX-2. Aspirin and other NSAIDs provided pain relief by blocking the effect of both of these enzymes without selectively targeting one COX enzyme over another. Considerable research was performed to determine which of these enzymes was most responsible for pain relief. It was found that COX-1 existed in all tissues, whereas COX-2 appeared to be restricted to specific organs and parts of the body, such as the brain, kidney, bones, testicles, ovaries, uterus, trachea and small intestines.
When the two different types of COX enzymes were discovered, it was unknown whether one or both played a larger role in the pain and inflammation process. In hopes of developing a more effective pain reliever, drug companies became very interested in developing new drugs that could block the COX-1 without blocking the COX-2 enzymes, or vice versa.
Read Next: Cox-1 vs. Cox-2