Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) used to treat ankylosing spondylitis (AS), colorectal adenomas, gouty arthritis, osteoarthritis (OA), and rheumatoid arthritis, among others. This drug possesses analgesic and antipyretic activities. This drug is a prodrug, its active metabolite is the sulfide form of the molecule. It acts by binding as an inhibitor to the prostaglandin G/H synthase 2. This results in the inhibition of the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 convert arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase, or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Sulindac (its sulfide metabolite) inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. This drug is administered as an oral tablet.

Sulindac Pathway (New) References