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Pathway Description
Prednicarbate Action Pathway
Homo sapiens
Drug Action Pathway
Prednicarbate is a relatively new topical corticosteroid. It displays similar potency as hydrocortisone and has a favorable benefit-risk ratio, with an inflammatory action similar to that of a medium potency corticosteroid, but with a low potential to cause skin atrophy. Since prednicarbate is a glucocorticoid receptor agonist. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence the effects of inflammation through vasoconstriction/dilation, pain sensitivity, and platelet aggregation. Prednicarbate also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases the concentrations of prostanoids mentioned calming inflammation. This molecule is administered as a topical cream or ointment.
References
Prednicarbate Pathway 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
Gupta AK, Chow M: A review of prednicarbate (Dermatop). Skin Therapy Lett. 2004 Dec-2005 Jan;9(10):5-6, 9.
Pubmed: 15657633
Boudinot FD, D'Ambrosio R, Jusko WJ: Receptor-mediated pharmacodynamics of prednisolone in the rat. J Pharmacokinet Biopharm. 1986 Oct;14(5):469-93. doi: 10.1007/BF01059656.
Pubmed: 2879901
Ikonomidis I, Tzortzis S, Lekakis J, Paraskevaidis I, Andreadou I, Nikolaou M, Kaplanoglou T, Katsimbri P, Skarantavos G, Soucacos P, Kremastinos DT: Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis. Heart. 2009 Sep;95(18):1502-7. doi: 10.1136/hrt.2009.168971. Epub 2009 May 28.
Pubmed: 19482847
Lange K, Gysler A, Bader M, Kleuser B, Korting HC, Schafer-Korting M: Prednicarbate versus conventional topical glucocorticoids: pharmacodynamic characterization in vitro. Pharm Res. 1997 Dec;14(12):1744-9. doi: 10.1023/a:1012183914011.
Pubmed: 9453063
Oeckinghaus A, Ghosh S. The NF-kB Family of Transcription Factors and Its Regulation. Cold Spring Harb Perspect Biol 1(4): a000034, 2009.
Kirschke E, Goswami D, Southworth D, Griffin P. R, Agard D. Glucocorticoid Receptor Function Regulated by Coordinated Action of the Hsp90 and Hsp70 Chaperone Cycles. Cell 157(7): 1685-1697, 2014.
Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of
inflammation. Nature Reviews Immunology 9: 62–70, 2009.
Liu T, Zhang L, Joo D, Sun S. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2: 17023, 2017.
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