NSAIDs

The enzyme PGH synthase catalyzes the conversion of arachidonic acid to PGH2, an essential step in prostaglandin biosynthesis. Mammalian cells contain two forms of PGH synthase called PGHS-1 and PGHS-2 (or Cox-1 and Cox-2, respectively).

Aspirin and other non-steroidal compounds, which target the PGH synthases, are called non-steroidal anti-inflammatory drugs (NSAIDs) because they help prevent formation of prostaglandins and thromboxanes, thus reducing pain and inflammation in the body.

Aspirin (acetylsalicylic acid) acts to inhibit both PGHS-1 and PGHS-2 by acetylating a specific serine residue in each enzyme, blocking access of arachidonate to the active site. The antiinflammatory and analgesic properties of aspirin arise from inhibition of PGHS-2. Inhibition of PGHS-1 leads to ulceration and other undesirable effects on the gastrointestinal system.

Ibuprofen acts more specifically on PGSH-2, but is less effective of an inhibitor than aspirin.

A new NSAID called Celebrex was released in 1998 for relief of arthritis pain. It binds 400-fold more tightly to PGHS-2 than to PGHS-1 so it should maximize the antiinflammatory and analgesic benefits while minimizing the undesirable effects.

See also: Eicosanoids, Prostaglandin Biosynthesis, Prostaglandins, Thromboxanes

INTERNET LINK: COX-2 Inhibitors