NSAIDs and COX-2 Inhibitors

Nonsteroidal anti-inflammatory drugs in the form of salicylates have been used for centuries for the control of pain and inflammation. Acetylsalicylic acid, aspirin, was the first of this class to be synthesized by Felix Hoffman in 1899 and thus became generally available for medical use. Since the profile of activity of this class was clearly different from the glucocorticoids, they were named ‘‘nonsteroidal anti-inflammatory drugs’’ (NSAIDs). In 1971, the pioneering work of Vane (1) demonstrated that aspirin inhibited the formation of prostaglandins via inhibition of the cyclooxygenase (COX) enzyme. COX is the enzyme responsible for the conversion of arachidonic acid, released from membrane phospholipids by the action of phopholipase, into the endoperoxide Prostaglandin G2 via the cyclooxygenase reaction, and subsequently via a hydroperoxidase-mediated conversion to Prostaglandin H2, the precursor to the wide range of prostanoids known today (Fig. 1). The bifunctional enzyme responsible for the conversion of arachidonic acid to PGH2 is colloquially referred to as ‘‘cyclooxygenase (COX)’’ although it is more correctly named ‘‘prostaglandin H2 synthase (PGHS).’’