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Pathway Description
Phenylbutazone Action Pathway (New)
Homo sapiens
Drug Action Pathway
Phenylbutazone is a synthetic nonsteroidal anti-inflammatory drug (NSAID) derived from pyrazolone. It is used to treat pain and inflammation, mostly backache, rheumatoid arthritis, and ankylosing spondylitis. This drug has anti-inflammatory, antipyretic, and analgesic activities. Its analgesic effect comes from its ability to reduce the production of prostaglandin H and prostacyclin. Prostaglandin is a molecule that is acting on a wide variety of cells such as vascular smooth muscle cells causing constriction or dilatation, on platelets causing aggregation or disaggregation, and on spinal neurons causing pain. Phenylbutazone binds and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide-mediated deactivation. Due to these two inactivations, the level of prostaglandins decreases and the inflammation is reduced in the surrounding tissues. Phenylbutazone is administered as an oral tablet.
References
Phenylbutazone Pathway (New) References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Reed GA, Griffin IO, Eling TE: Inactivation of prostaglandin H synthase and prostacyclin synthase by phenylbutazone. Requirement for peroxidative metabolism. Mol Pharmacol. 1985 Jan;27(1):109-14.
Pubmed: 3917545
Marnett LJ, Siedlik PH, Ochs RC, Pagels WR, Das M, Honn KV, Warnock RH, Tainer BE, Eling TE: Mechanism of the stimulation of prostaglandin H synthase and prostacyclin synthase by the antithrombotic and antimetastatic agent, nafazatrom. Mol Pharmacol. 1984 Sep;26(2):328-35.
Pubmed: 6434940
Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P: Phenylbutazone in the horse: a review. J Vet Pharmacol Ther. 1986 Mar;9(1):1-25. doi: 10.1111/j.1365-2885.1986.tb00008.x.
Pubmed: 3517382
Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT: Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis. Res Vet Sci. 2005 Apr;78(2):189-92. doi: 10.1016/j.rvsc.2004.07.006.
Pubmed: 15563928
Arifah AK, Lees P: Pharmacodynamics and pharmacokinetics of phenylbutazone in calves. J Vet Pharmacol Ther. 2002 Aug;25(4):299-309. doi: 10.1046/j.1365-2885.2002.00421.x.
Pubmed: 12213119
Takada Y, Bhardwaj A, Potdar P, Aggarwal BB: Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene. 2004 Dec 9;23(57):9247-58. doi: 10.1038/sj.onc.1208169.
Pubmed: 15489888
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