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Chemical Compound Review

Aphrodil     3-[2-ethoxy-5-(4- methylpiperazin-1...

Synonyms: Caverta, Revatio, sildenafil, CHEMBL192, Aphrodil (TN), ...
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Disease relevance of C07259


Psychiatry related information on C07259


High impact information on C07259


Chemical compound and disease context of C07259


Biological context of C07259


Anatomical context of C07259

  • Here, we show that blocking the intrinsic catabolism of cGMP with an oral phosphodiesterase-5A (PDE5A) inhibitor (sildenafil) suppresses chamber and myocyte hypertrophy, and improves in vivo heart function in mice exposed to chronic pressure overload induced by transverse aortic constriction [3].
  • By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy [24].
  • In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase-2 expression, thereby reducing the suppressive machinery of CD11b(+)/Gr-1(+) myeloid-derived suppressor cells (MDSCs) recruited by growing tumors [24].
  • Results: Lower esophageal sphincter tone, residual pressure, and wave amplitude after sildenafil showed a significant decrease compared with both the basal period and the placebo group, with a marked interpatient variability [25].
  • Oral sildenafil is an effective and well-tolerated treatment for erectile dysfunction caused by spinal cord injury [26].

Associations of C07259 with other chemical compounds


Gene context of C07259


Analytical, diagnostic and therapeutic context of C07259

  • For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5) [19].
  • Sildenafil and ocular perfusion [37].
  • We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, and mixed causes [19].
  • INTERVENTIONS: All patients underwent 2 symptom-limited supine bicycle echocardiograms separated by an interval of 1 to 3 days after receiving a single dose of sildenafil (50 or 100 mg) or placebo 1 hour before each exercise test [20].
  • CONCLUSION: In men with stable CAD, sildenafil had no effect on symptoms, exercise duration, or presence or extent of exercise-induced ischemia, as assessed by exercise echocardiography [20].


  1. Acute myocardial infarction after the use of sildenafil. Arora, R.R., Timoney, M., Melilli, L. N. Engl. J. Med. (1999) [Pubmed]
  2. Hemodynamic effects of sildenafil in men with severe coronary artery disease. Herrmann, H.C., Chang, G., Klugherz, B.D., Mahoney, P.D. N. Engl. J. Med. (2000) [Pubmed]
  3. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Takimoto, E., Champion, H.C., Li, M., Belardi, D., Ren, S., Rodriguez, E.R., Bedja, D., Gabrielson, K.L., Wang, Y., Kass, D.A. Nat. Med. (2005) [Pubmed]
  4. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial. Sildenafil Diabetes Study Group. Rendell, M.S., Rajfer, J., Wicker, P.A., Smith, M.D. JAMA (1999) [Pubmed]
  5. Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: a double-blind, placebo-controlled, randomized, crossover trial. Parker, J.D., Bart, B.A., Webb, D.J., Koren, M.J., Siegel, R.L., Wang, H., Malhotra, B., Jen, F., Glue, P. Crit. Care Med. (2007) [Pubmed]
  6. Sildenafil in the treatment of erectile dysfunction. Meikle, A.W., Arver, S. N. Engl. J. Med. (1998) [Pubmed]
  7. Sildenafil use, sexual risk behavior, and risk for sexually transmitted diseases, including HIV infection. Swearingen, S.G., Klausner, J.D. Am. J. Med. (2005) [Pubmed]
  8. Use of sildenafil for safe improvement of erectile function and quality of life in men with New York Heart Association classes II and III congestive heart failure: a prospective, placebo-controlled, double-blind crossover trial. Webster, L.J., Michelakis, E.D., Davis, T., Archer, S.L. Arch. Intern. Med. (2004) [Pubmed]
  9. Transient global amnesia after sildenafil (Viagra) use. Savitz, S.A., Caplan, L.R. Neurology (2002) [Pubmed]
  10. Effectiveness of sildenafil in treating erectile dysfunction in PTSD patients: a double-blind, placebo-controlled crossover study. Orr, G., Weiser, M., Polliack, M., Raviv, G., Tadmor, D., Grunhaus, L. Journal of clinical psychopharmacology. (2006) [Pubmed]
  11. A stimulatory role for cGMP-dependent protein kinase in platelet activation. Li, Z., Xi, X., Gu, M., Feil, R., Ye, R.D., Eigenthaler, M., Hofmann, F., Du, X. Cell (2003) [Pubmed]
  12. Sildenafil in primary pulmonary hypertension. Prasad, S., Wilkinson, J., Gatzoulis, M.A. N. Engl. J. Med. (2000) [Pubmed]
  13. Increased glomerular filtration rate in kidney-transplant recipients who take sildenafil. Rostaing, L., Tran-Van, T., Ader, J.L. N. Engl. J. Med. (2000) [Pubmed]
  14. Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Bender, A.T., Beavo, J.A. Pharmacol. Rev. (2006) [Pubmed]
  15. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Ghofrani, H.A., Wiedemann, R., Rose, F., Schermuly, R.T., Olschewski, H., Weissmann, N., Gunther, A., Walmrath, D., Seeger, W., Grimminger, F. Lancet (2002) [Pubmed]
  16. Sex and the patient with cardiovascular risk factors: focus on sildenafil. Kloner, R.A. Am. J. Med. (2000) [Pubmed]
  17. Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Schermuly, R.T., Kreisselmeier, K.P., Ghofrani, H.A., Yilmaz, H., Butrous, G., Ermert, L., Ermert, M., Weissmann, N., Rose, F., Guenther, A., Walmrath, D., Seeger, W., Grimminger, F. Am. J. Respir. Crit. Care Med. (2004) [Pubmed]
  18. Efficacy of oral sildenafil in the treatment of erectile dysfunction in diabetic men with positive response to intracavernosal injection of alprostadil. Lepore, G., Nosari, I. Diabetes Care (2001) [Pubmed]
  19. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. Goldstein, I., Lue, T.F., Padma-Nathan, H., Rosen, R.C., Steers, W.D., Wicker, P.A. N. Engl. J. Med. (1998) [Pubmed]
  20. Cardiovascular effects of sildenafil during exercise in men with known or probable coronary artery disease: a randomized crossover trial. Arruda-Olson, A.M., Mahoney, D.W., Nehra, A., Leckel, M., Pellikka, P.A. JAMA (2002) [Pubmed]
  21. Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial. Nurnberg, H.G., Hensley, P.L., Gelenberg, A.J., Fava, M., Lauriello, J., Paine, S. JAMA (2003) [Pubmed]
  22. Increased bioavailability of sildenafil in Mexican men. Flores-Murrieta, F.J., Castañeda-Hernández, G., Granados-Soto, V., Herrera, J.E. JAMA (2000) [Pubmed]
  23. Safe sex for men with coronary artery disease: exercise, sildenafil, and risk of cardiac events. Marwick, T.H. JAMA (2002) [Pubmed]
  24. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. Serafini, P., Meckel, K., Kelso, M., Noonan, K., Califano, J., Koch, W., Dolcetti, L., Bronte, V., Borrello, I. J. Exp. Med. (2006) [Pubmed]
  25. Effects of sildenafil on esophageal motility of patients with idiopathic achalasia. Bortolotti, M., Mari, C., Lopilato, C., Porrazzo, G., Miglioli, M. Gastroenterology (2000) [Pubmed]
  26. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Sildenafil Study Group. Giuliano, F., Hultling, C., El Masry, W.S., Smith, M.D., Osterloh, I.H., Orr, M., Maytom, M. Ann. Neurol. (1999) [Pubmed]
  27. Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells. Sarfati, M., Mateo, V., Baudet, S., Rubio, M., Fernandez, C., Davi, F., Binet, J.L., Delic, J., Merle-Beral, H. Blood (2003) [Pubmed]
  28. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Ayala, J.E., Bracy, D.P., Julien, B.M., Rottman, J.N., Fueger, P.T., Wasserman, D.H. Diabetes (2007) [Pubmed]
  29. Multiple conformations of phosphodiesterase-5: implications for enzyme function and drug development. Wang, H., Liu, Y., Huai, Q., Cai, J., Zoraghi, R., Francis, S.H., Corbin, J.D., Robinson, H., Xin, Z., Lin, G., Ke, H. J. Biol. Chem. (2006) [Pubmed]
  30. Effect of sildenafil and rolipram on adrenergic responses in isolated human and monkey corpus cavernosum. Lau, L.C., Adaikan, P.G. Eur. Urol. (2007) [Pubmed]
  31. A rational combination pharmacotherapy in men with erectile dysfunction who initially failed to oral sildenafil citrate alone: a pilot study. Taneja, R. J. Sex. Med (2007) [Pubmed]
  32. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. Das, A., Xi, L., Kukreja, R.C. J. Biol. Chem. (2005) [Pubmed]
  33. The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a protein kinase G/MAPK pathway. Pyriochou, A., Zhou, Z., Koika, V., Petrou, C., Cordopatis, P., Sessa, W.C., Papapetropoulos, A. J. Cell. Physiol. (2007) [Pubmed]
  34. Postnatal maturation of phosphodiesterase 5 (PDE5) in piglet pulmonary arteries: activity, expression, effects of PDE5 inhibitors, and role of the nitric oxide/cyclic GMP pathway. Moreno, L., Losada, B., Cogolludo, A., Lodi, F., Lugnier, C., Villamor, E., Moro, M., Tamargo, J., Pérez-Vizcaíno, F. Pediatr. Res. (2004) [Pubmed]
  35. Antioxidant treatment associated with sildenafil reduces monocyte activation and markers of endothelial damage in patients with diabetic erectile dysfunction: a double-blind, placebo-controlled study. Morano, S., Mandosi, E., Fallarino, M., Gatti, A., Tiberti, C., Sensi, M., Gandini, L., Buchetti, B., Lenti, L., Jannini, E.A., Lenzi, A. Eur. Urol. (2007) [Pubmed]
  36. Sildenafil-mediated neovascularization and protection against myocardial ischaemia reperfusion injury in rats: role of VEGF/angiopoietin-1. Koneru, S., Varma Penumathsa, S., Thirunavukkarasu, M., Vidavalur, R., Zhan, L., Singal, P.K., Engelman, R.M., Das, D.K., Maulik, N. J. Cell. Mol. Med. (2008) [Pubmed]
  37. Sildenafil and ocular perfusion. Sponsel, W.E., Paris, G., Sandoval, S.S., Sanford, D.K., Harrison, J.M., Elliott, W.R., Trigo, Y. N. Engl. J. Med. (2000) [Pubmed]
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