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. | 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> | 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). | 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> | It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.<ref name="a43">PMID:10773497</ref> | ||
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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>. | 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> | 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 == | ||
<references/> | <references/> | ||
Latest revision as of 12:01, 21 January 2024
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:
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ReferencesReferences
- ↑ Mitchell JA, Akarasereenont P, Thiemermann C, Flower RJ, Vane JR. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693-7. PMID:8265610 doi:10.1073/pnas.90.24.11693
- ↑ Dastidar SG, Ganguly K, Chaudhuri K, Chakrabarty AN. The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis. Int J Antimicrob Agents. 2000 Apr;14(3):249-51. PMID:10773497 doi:10.1016/s0924-8579(99)00159-4
- ↑ Sandri A. [Diclofenac: update on tolerableness and spinal anti-inflammatory action]. Minerva Med. 2014 Aug;105(4):313-8 PMID:25078485
- ↑ Sandri A. Spinal antinflammatory action of Diclofenac. Minerva Med. 2016 Jun;107(3):167-72. Epub 2016 Mar 25 PMID:27014880
- ↑ Scholer DW, Ku EC, Boettcher I, Schweizer A. Pharmacology of diclofenac sodium. Am J Med. 1986 Apr 28;80(4B):34-8. PMID:3085490 doi:10.1016/0002-9343(86)90077-x
- ↑ Voilley N, de Weille J, Mamet J, Lazdunski M. Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors. J Neurosci. 2001 Oct 15;21(20):8026-33. PMID:11588175 doi:10.1523/JNEUROSCI.21-20-08026.2001