Diclofenac
Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. See also [1]. Diclofenac is believed to work by decreasing the production of prostaglandins, like other drugs in this class. As with most NSAIDs, the primary mechanism responsible for its anti-inflammatory, antipyretic, and analgesic action is thought to be inhibition of prostaglandin synthesis through cyclooxygenase inhibition. Diclofenac inhibits COX-1 and COX-2 with relative equipotency.[1] Structure of Aspirin Acetylated Cyclooxygenase-1 in Complex with Diclofenac (3n8y). Diclofenac binding site. The main target in inhibition of prostaglandin synthesis appears to be the transiently expressed prostaglandin-endoperoxide synthase-2 (PGES-2) also known as cycloxygenase-2 (COX-2). It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.[2] Diclofenac has a relatively high lipid solubility, making it one of the few NSAIDs that are able to enter the brain by crossing the blood-brain barrier. In the brain, too, it is thought to exert its effect through inhibition of COX-2.[3] In addition, it may have effects inside the spinal cord.[4]. It also may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain its high potency – it is the most potent NSAID on a broad basis.[5] Crystal structure of the complex formed between phospholipase A2 and diclofenac (2b17). Diclofenac binding site. Besides the COX and phospholipase A2 inhibition, a number of other molecular targets of diclofenac possibly contributing to its pain-relieving actions have recently been identified. These include:
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