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Pathway Description
Sildenafil Action Pathway
Homo sapiens
Drug Action Pathway
Sildenafil is a phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction.
Sexual stimulation causes the release of nitric oxide (NO) from nerves and endothelial cells into the penis. NO activates the enzyme guanylate cyclase.2 The activation of this enzyme is followed by the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP), activating a cascade of protein kinase-dependent phosphorylation events in smooth muscles, ultimately resulting in the dephosphorylation of myosin light chains within smooth muscle. This activity causes the relaxation of smooth muscle within blood vessels, resulting in the desired vasodilatory effect. Phosphodiesterase-5 breaks down cGMP to GMP. Sildenafil inhibits phosphodiesterase-5, preventing the breakdown of cGMP. This increases the concentration of cGMP, increasing the vasodilation and improving blood flow leading to penile erection.
References
Sildenafil Pathway References
Cruz-Burgos M, Losada-Garcia A, Cruz-Hernández CD, Cortés-Ramírez SA, Camacho-Arroyo I, Gonzalez-Covarrubias V, Morales-Pacheco M, Trujillo-Bornios SI and Rodríguez-Dorantes M (2021) New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil. Front. Oncol. 11:627229. doi: 10.3389/fonc.2021.627229
Wishart, D., Knox, C., Guo, A., Shrivastava, S., Hassanali, M., Stothard, P., . . . Woolsey, J. (2005, June). Sildenafil. Retrieved July 24, 2021, from https://go.drugbank.com/drugs/DB00203
Smith BP, Babos M: Sildenafil
Pubmed: 32644404
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
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