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] (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)