Naproxen

OVERVIEW

Naproxen (nah-PROK-sin) is a white to off-white odorless crystalline solid sold under a variety of commercial names, including Aleve®, Anaprox®, Bonyl®, Calosen®, Diocodal®, Naprosyn®, Naprelan®, Proxen®, and Veradol®. It is a nonsteroidal anti-inflammatory drug (NSAID) used as an analgesic (pain reliever) and antipyretic (fever-reducing compound). The compound is also available as a sodium salt, which is more readily absorbed in the gastrointestinal tract. Nonsteroidal anti-inflammatory drugs are compounds used to reduce pain, fever, and inflammation without the use of steroids (thus, nonsteroidal) by inhibiting the action of an enzyme needed to produce these results in the body. Other examples of NSAIDs are aspirin, ibuprofen, and prednisone.

KEY FACTS

OTHER NAMES:

(S)-6-methoxy-α-methyl-2-naphthaleneacetic acid; d-2-(6-methoxy-2-naphthyl)-propionic acid

FORMULA:

C₁₄H₁₄O₃

ELEMENTS:

Carbon, hydrogen, oxygen

COMPOUND TYPE:

Carboxylic acid (organic)

STATE:

Solid

MOLECULAR WEIGHT:

230.26 g/mol

MELTING POINT:

155°C (311°F)

BOILING POINT:

Not applicable

SOLUBILITY:

Insoluble in water; soluble in methyl alcohol and chloroform

HOW IT IS MADE

Naproxen is prepared by treating 2-methoxynaphthalene with a derivative of propanoic acid (CH₃CH₂COOH). 2-methoxynaphthalene has a structure very similar to that of naproxen and requires only the addition of the propanoyl group (-CH₂CH₂COOH) provided by propanoic acid. The reaction is fairly straightforward but includes one important consideration. Naproxen is a chiral compound, meaning that it can exist in one of two isomeric forms. The two forms are a "right-handed" form (designated as the R form) and a "left-handed" form (designated as the S form). As is the case with many organic compounds, the two chiral forms of naproxen have very different biological activities. Specifically, the S-form of naproxen is 28 times as effective as the R-form in achieving the analgesic, antipyretic, and anti-inflammatory results expected from the compound. Early methods for preparing naproxen resulted in the formation of a racemic mixture of R and S forms. A racemic mixture is one that contains both of the isomeric forms in which a compound can occur. The two parts of the racemic mixture, the R and S forms, then had to be separated from each other. Researchers have now developed a method of manufacture that produces essentially pure S naproxen, avoiding the time-consuming and costly process of separation previously required.

Interesting Facts

• The U.S. Food and Drug Administration first approved the sale of naproxen as an over-the-counter medication (one that does not require a prescription) in 1994.

COMMON USES AND POTENTIAL HAZARDS

Naproxen is commonly used to treat the pain and stiffness caused by conditions such as arthritis, inflammation of the joints, gout, tendonitis, and bursitis. It achieves this result by inhibiting the activity of an enzyme called cycloox-ygenase 2 (COX-2). COX-2 facilitates the production of a class of compounds in the body known as prostaglandins. Prostaglandins are produced when the body is injured, causing the pain and inflammation usually associated with an injury. Naproxen blocks the active site on a COX-2 molecule that catalyzes the formation of COX-2 molecules with the result: no COX-2; no prostaglandins; no pain and inflammation. Interestingly enough, a very similar enzyme called cyclooxygenase 1 (COX-1) also exists in the body. COX-1, however, has a different set of functions that have nothing to do with the production of pain and inflammation. Since naproxen inhibits COX-2, but not COX-1, it is known as a selective inhibitor NSAID.

A number of relatively minor side effects have been reported for naproxen, including headache, dizziness, drowsiness, itching, ringing in the ears, and minor gastrointestinal discomfort that may include heartburn, abdominal pain, nausea, constipation, and diarrhea. More serious problems have also been reported, including gastrointestinal complications such as bleeding and ulceration (bleeding sores) of the stomach and intestines. In some cases, the drug has been responsible for the hospitalization of users.

Care needs to be taken when combining naproxen with other medications. Known adverse drug interactions can occur with aspirin, methotrexate, ACE inhibitors (for high blood pressure), furosemide, lithium, and warfarin (a blood thinner). An overdose of naproxen may cause dizziness, drowsiness, and gastrointestinal problems. High blood pressure, kidney failure, and coma may occur, but are rare.

Words to Know

CATALYST

A material that increases the rate of a chemical reaction without undergoing any change in its own chemical structure.

ISOMER

One of two or more forms of a chemical compound with the same molecular formula, but different structural formulas and different chemical and physical properties.

FOR FURTHER INFORMATION

Buschmann, Helmut, et al. Analgesics: From Chemistry and Pharmacology to Clinical Application. New York: Wiley-VCH, 2002.

"Naproxen." World of Molecules. http://www.worldofmolecules.com/drugs/naproxen.htm (accessed on October 17, 2005).

Omudhome, Ogbru. "Naproxen Center." http://www.medicinenet.com/naproxen/article.htm (accessed on October 17, 2005).

"Product Monograph: Anaprox®; Anaprox® DS." Roche. http://www.rochecanada.com/pdf/Anaprox%20PM%20E.pdf (accessed on October 17, 2005).

naproxen (nă-proks-ĕn) n. an analgesic drug that also reduces inflammation and fever (see NSAID). It is administered by mouth to treat rheumatoid arthritis, ankylosing spondylitis, and gout. It may be used in combination with misoprostol (as Napratec) to prevent gastrointestinal bleeding. Trade names: Naprosyn, Nycopren, Synflex.