Diclofenac: Difference between revisions
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<StructureSection load='' size='340' side='right' caption=' | <StructureSection load='' size='340' side='right' caption='Diclofenac' scene='97/974935/Cv/1'> | ||
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 [https://en.wikipedia.org/wiki/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 [https://en.wikipedia.org/wiki/Diclofenac]. | ||
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.<ref name="a42">PMID:8265610</ref> <scene name='97/974935/Cv/3'>Structure of Aspirin Acetylated Cyclooxygenase-1 in Complex with Diclofenac</scene> ([[3n8y]]). <scene name='97/974935/Cox_binding_site/1'>Diclofenac binding site</scene>. | |||
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.<ref name="a43">PMID:10773497</ref> | |||
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.<ref name="a44">PMID:25078485</ref> In addition, it may have effects inside the spinal cord.<ref name="a45">PMID:27014880</ref>. | |||
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.<ref name="a46">PMID:3085490</ref> <scene name='97/974935/Cv/2'>Crystal structure of the complex formed between phospholipase A2 and diclofenac</scene> ([[2b17]]). <scene name='97/974935/Binding_site/1'>Diclofenac binding site</scene>. | |||
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)<ref name="a48">PMID:11588175</ref> | |||
*Positive allosteric modulation of KCNQ- and BK-potassium channels (diclofenac opens these channels, leading to hyperpolarization of the cell membrane). See [[Potassium Channel]]. | |||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
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