Diclofenac
From Proteopedia
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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References
- ↑ 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
