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] (3n8y). .
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] (2b17). .
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:
- Blockage of voltage-dependent sodium channels (after activation of the channel, diclofenac inhibits its reactivation also known as phase inhibition)
- Blockage of acid-sensing ion channels (ASICs)[6]
- Positive allosteric modulation of KCNQ- and BK-potassium channels (diclofenac opens these channels, leading to hyperpolarization of the cell membrane). See Potassium Channel.
