Skip to main content
SpringerLink
Log in

The discovery and development of Viagra® (sildenafil citrate)

  • Chapter
Sildenafil

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

Sildenafil citrate (UK-92,480, Viagra®) is a selective inhibitor of phosphodiesterase type 5 (PDE5) and acts on the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway [1, 2]. UK-92,480 was first synthesised in the Sandwich laboratories of Pfizer Ltd, UK in 1989, and resulted from a discovery programme aimed at developing a selective inhibitor of PDE5. The origins of the project that eventually led to the discovery and development of Viagra date from around the mid 1980s. At this time, scientists working at the Pfizer European Research Centre were interested in potential new approaches to the treatment of several cardiovascular diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Jeremy JY, Ballard SA, Naylor AM, Miller MAW, Angelini GD (1997) Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol 79: 958–963

    Article  PubMed  CAS  Google Scholar 

  2. Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C (1996) Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8: 47–52

    PubMed  CAS  Google Scholar 

  3. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329: 2002–2012

    Article  PubMed  CAS  Google Scholar 

  4. Hare TM, Colucci WS (1995) Role of nitric oxide in the regulation of myocardial function. Prog Cardiovasc Dis 38: 155–166

    Article  CAS  Google Scholar 

  5. Beavo JA (1995) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 75: 725–748

    PubMed  CAS  Google Scholar 

  6. Terrett N, Bell A, Brown D, Ellis P (1996) Sildenafil (Viagra), a potent and selective inhibitor of type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg Med Chem Lett 6: 1819–1824

    Article  Google Scholar 

  7. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM (1998) Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159: 2164–2171

    Article  PubMed  CAS  Google Scholar 

  8. Lue TF (2000) Erectile dysfunction. N Engl J Med 342: 1802–1813

    Article  PubMed  CAS  Google Scholar 

  9. Jackson G, Benjamin N, Jackson N, Allen MJ (1999) Effects of sildenafil citrate on human hemodynamics. Am J Cardiol 83: 13C–20C

    Article  PubMed  CAS  Google Scholar 

  10. Wallis RM, Corbin JD, Francis SH, Ellis P (1999) Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol 83: 3C–12C

    Article  PubMed  CAS  Google Scholar 

  11. Muirhead GJ, Rance DJ, Walker DK, Wastall P (2002) Comparative human pharmacokinetics and metabolism of single-dose oral and intravenous sildenafil. Br J Clin Pharmacol 53 (Suppl 1): 13S–20S

    Article  PubMed  CAS  Google Scholar 

  12. Nichols DJ, Muirhead GJ, Harness JA (2002) Pharmacokinetics of sildenafil citrate after single oral doses in healthy male subjects: absolute bioavailability, food effects and dose proportionality. Br J Clin Pharmacol 53: 5S–12S

    Article  PubMed  CAS  Google Scholar 

  13. Webb DJ, Freestone S, Allen MJ, Muirhead GJ (1999) Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol 83: 21C–28C

    Article  PubMed  CAS  Google Scholar 

  14. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ (1996) Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol 78: 257–261

    Article  PubMed  CAS  Google Scholar 

  15. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A (1997) The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49: 822–830

    Article  PubMed  CAS  Google Scholar 

  16. Montorsi F, McDermott TE, Morgan R, Olsson A, Schultz A, Kirkeby HJ, Osterloh IH (1999) Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies. Urology 53: 1011–1018

    Article  PubMed  CAS  Google Scholar 

  17. Dinsmore WW, Hodges M, Hargreaves C, Osterloh IH, Smith MD, Rosen RC (1999) Sildenafil citrate (VIAGRA) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects. Urology 53: 800–805

    Article  PubMed  CAS  Google Scholar 

  18. Kloner RA, Brown M, Prisant LM, Collins M (2000) Efficacy and safety of Viagra (sildenafil citrate) in patients with erectile dysfunction taking concomitant antihypertensive therapy. Am J Hypertens 14: 70–73

    Article  Google Scholar 

  19. Conti CR, Pepine CJ, Sweeney M (1999) Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. Am J Cardiol 83: 29C–34C

    Article  PubMed  CAS  Google Scholar 

  20. Olsson AM, Persson CA (2001) Efficacy and safety of sildenafil citrate for the treatment of erectile dysfunction in men with cardiovascular disease. Int J Clin Pract 55: 171–176

    PubMed  CAS  Google Scholar 

  21. Rendell MS, Rajfer J, Wicker PA, Smith MD, for the Sildenafil Diabetes Study Group (1999) Sildenafil for treatment of erectile dysfunction in men with diabetes. JAMA 281: 421–426

    Article  PubMed  CAS  Google Scholar 

  22. Giuliano F, Hultling C, El Masry WS, Smith MD, Osterloh IH, Orr M, Maytom M (1999) Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Ann Neurol 46: 15–21

    Article  PubMed  CAS  Google Scholar 

  23. Derry FA, Dinsmore WW, Fraser M, Gardner BP, Glass CA, Maytom MC, Smith MD (1998) Efficacy and safety of oral sildenafil (VIAGRA) in men with erectile dysfunction caused by spinal cord injury. Neurology 51: 1629–1633

    Article  PubMed  CAS  Google Scholar 

  24. Zippe CD, Kedia AW, Kedia K, Nelson DR, Agarwal A (1998) Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra). Urology 52: 963–966

    Article  PubMed  CAS  Google Scholar 

  25. Lowentritt BH, Scardino PT, Miles BJ, Orejuela FJ, Schatte EC, Slawin KM, Elliott SP, Kim ED (1999) Sildenafil citrate after radical retropubic prostatectomy. J Urol 162: 1614–1617

    Article  PubMed  CAS  Google Scholar 

  26. Wagner G, Montorsi F, Auerbach S, Collins M (2001) Sildenafil citrate (VIAGRA) improves erectile function in elderly patients with erectile dysfunction: a subgroup analysis. J Gerontol A Biol Sci Med Sci 56: M113—M119

    Article  PubMed  CAS  Google Scholar 

  27. Hussain IF, Brady CM, Swinn MJ, Mathias CJ, Fowler CJ (2001) Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson’s disease or multiple system atrophy with observations on orthostatic hypotension. J Neurol Neurosurg Psychiatry 71: 371–374

    Article  PubMed  CAS  Google Scholar 

  28. Fowler C, Miller J, Sharief M (1999) Viagra (sildenafil citrate) for the treatment of erectile dysfunction in men with multiple sclerosis. Ann Neurol 46: 497

    Google Scholar 

  29. Chen J, Mabjeesh NJ, Greenstein A, Nadu A, Matzkin H (2001) Clinical efficacy of sildenafil in patients on chronic dialysis. J Urol 165: 819–821

    Article  PubMed  CAS  Google Scholar 

  30. Rosas SE, Wasserstein A, Kobrin S, Feldman HI (2001) Preliminary observations of sildenafil treatment for erectile dysfunction in dialysis patients. Am J Kidney Dis 37: 134–137

    Article  PubMed  CAS  Google Scholar 

  31. Prieto Castro RM, Anglada Curado FJ, Regueiro Lopez JC, Leva Vallejo ME, Molina Sanchez J, Saceda Lopez JL, Requena Tapia MJ (2001) Treatment with sildenafil citrate in renal transplant patients with erectile dysfunction. BJU Int 88: 241–243

    Article  PubMed  CAS  Google Scholar 

  32. Chait J, Kobashigawa J, Chuang J, Moriguchi J, Kawata N, Laks H (1999) Efficacy and safety of sildenafil citrate (Viagra) in male heart transplant patients. J Heart Lung Transplant 18: 58

    Google Scholar 

  33. Wagoner LE, Giesting RM, Bell BJ, McGuire NC, Abraham WT (1999) Is Viagra (sildenafil) safe and effective in cardiac transplant recipients? Transplantation 67: S102

    Article  Google Scholar 

  34. Webster L, Michelakis E, Davis T, Tsuyuki R, Archer S (2002) Sildenafil is safe and effective treatment for erectile dysfunction in males with NYHA class II-III congestive heart failure. Circulation 106 (Suppl. 2): 11–469

    Google Scholar 

  35. Seidman SN, Roose SP, Menza MA, Shabsigh R, Rosen RC (2001) Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate. Am J Psychiatry 158: 1623–1630

    Article  PubMed  CAS  Google Scholar 

  36. Morales A, Gingell C, Collins M, Wicker PA, Osterloh IH (1998) Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res 10: 69–74

    Article  PubMed  CAS  Google Scholar 

  37. Laties AM, Zrenner E (2002) Viagra® (sildenafil citrate) and ophthalmology. Prog Retin Eye Res 21: 485–506

    Article  PubMed  CAS  Google Scholar 

  38. Corbin JD, Francis SH (2002) Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract 56: 453–459

    PubMed  CAS  Google Scholar 

  39. Padma-Nathan H, Eardley I, Kloner RA, Laties AM, Montorsi F (2002) A 4-year update on the safety of sildenafil citrate (Viagra®). Urology 60 (Suppl. 2B): 67–90

    Article  PubMed  Google Scholar 

  40. Sadovsky R, Miller T, Moskowitz M, Hackett G (2001) Three-year update of sildenafil citrate (Viagra) efficacy and safety. Int J Clin Pract 55: 115–128

    PubMed  CAS  Google Scholar 

  41. Shakir SAW, Wilton LV, Boshier A, Layton D, Heeley E (2001) Cardiovascular events in users of sildenafil: results from first phase of prescription event monitoring in England. BMJ 322: 651–652

    Article  PubMed  CAS  Google Scholar 

  42. Zusman R, Collins M (1999) Effect of sildenafil on blood pressure in men with erectile dysfunction taking concomitant antihypertensive medications. J Am Coll Cardiol 33: 238A

    Google Scholar 

  43. Zusman RM, Morales A, Glasser DB, Osterloh IH (1999) Overall cardiovascular profile of sildenafil citrate. Am J Cardiol 83: 35C–44C

    Article  PubMed  CAS  Google Scholar 

  44. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA (1998) Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 338: 1397–1404

    Article  PubMed  CAS  Google Scholar 

  45. Fagelman E, Fagelman A, Shabsigh R (2001) Efficacy, safety, and use of sildenafil in urologic practice. Urology 57: 1141–1144

    Article  PubMed  CAS  Google Scholar 

  46. Marks LS, Duda C, Dorey FJ, Macairan ML, Santos PB (1999) Treatment of erectile dysfunction with sildenafil. Urology 53: 19–24

    Article  PubMed  CAS  Google Scholar 

  47. Jarow JP, Burnett AL, Geringer AM (1999) Clinical efficacy of sildenafil citrate based on etiology and response to prior treatment. J Urol 162: 722–725

    Article  PubMed  CAS  Google Scholar 

  48. Moreira SG, Brannigan RE, Spitz A, Orejuela FJ, Lipshultz LI, Kim ED (2000) Side-effect profile of sildenafil citrate (Viagra) in clinical practice. Urology 56: 474–476

    Article  PubMed  Google Scholar 

  49. Moore R, Edwards J, McQuay H (2002) Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical trial reports. BMC Urol 2: 1–12

    Article  Google Scholar 

  50. Fink HA, Mac Donald R, Rutks IR, Nelson DB, Wilt TJ (2002) Sildenafil for male erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med 162: 1349–1360

    Article  PubMed  CAS  Google Scholar 

  51. Carson CC, Burnett AL, Levine LA, Nehra A (2002) The efficacy of sildenafil citrate (Viagra®) in clinical populations: an update. Urology 60 (Suppl 2B): 12–27

    Article  PubMed  Google Scholar 

  52. Berman JR, Berman LA, Toler SM, Gill J, Haughie S for the Sildenafil Study Group (2003) Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo-controlled study. J Urol 170: 2333–2338

    Article  PubMed  CAS  Google Scholar 

  53. Caruso S, Intelisano G, Lupo L, Agnello C (2001) Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, cross-over, placebo-controlled study. Br J Obs Gynaecol 108: 623–628

    CAS  Google Scholar 

  54. Nurnberg H, Hensley P, Lauriello J, Parker L, Keith S (1999) Sildenafil for women patients with antidepressant-induced sexual dysfunction. Psychiatr Sery 50: 1076–1078

    CAS  Google Scholar 

  55. Mark A, Shifren J (2003) Medical therapy for female sexual dysfunction. Prim Care Update Ob/Gyns 10: 40–43

    Article  Google Scholar 

  56. Reffelmann T, Kloner RA (2003) Therapeutic potential of phosphodiesterase 5 inhibition fn for cardiovascular disease. Circulation 108: 239–244

    Article  PubMed  Google Scholar 

  57. Zhang R, Wang Y, Zhang L, Zhang Z, Tsang W, Lu M, Zhang L, Chopp M (2002) Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 33: 2675–2680

    Article  PubMed  CAS  Google Scholar 

  58. Vlachopoulos C, O’Rourke MF, Hirata K (2001) Sildenafil (Viagra®) improves the elastic properties of the aorta. Am J Hypertens 14: 6A

    Google Scholar 

  59. Mahmud A, Hennessy M, Feely J (2001) Effect of sildenafil on blood pressure and arterial wave reflection in treated hypertensive men. J Hum Hypertens 15: 707–713

    Article  PubMed  CAS  Google Scholar 

  60. Lepore JJ, Maroo A, Pereira NL, Ginns LC, Dec GW, Zapol WM, Bloch KD, Semigran MJ (2002) Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol 90: 677–680

    Article  PubMed  CAS  Google Scholar 

  61. Watanabe H, Ohashi K, Takeuchi K, Yamashita K, Yokoyama T, Tran QK, Satoh H, Terada H, Ohashi H, Hayashi H (2002) Sildenafil for primary and secondary pulmonary hypertension. Clin Pharmacol Ther 71: 398–402

    Article  PubMed  Google Scholar 

  62. Abrams D, Schulze-Neick I, Magee A (2000) Sildenafil as a selective pulmonary vasodilator in childhood primary pulmonary hypertension. Heart 82: E4

    Article  Google Scholar 

  63. Carroll WD, Dhillon R (2003) Sildenafil as a treatment for pulmonary hypertension. Arch Dis Child 88: 827–828

    Article  PubMed  CAS  Google Scholar 

  64. Ghofrani HA, Rose F, Schermuly RT, Olschewski H, Wiedemann R, Kreckel A, Weissmann N, Ghofrani S, Enke B, Seeger W, Grimminger F (2003) Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 42: 158–164

    Article  PubMed  CAS  Google Scholar 

  65. Hirata K, Adji A, Vlachopoulos C, O’Rourke MF (2003) Sildenafil improves left ventricular systolic function in patients with congestive heart failure: the role of wave reflections. J Am Coll Cardiol 41 (Suppl A): 264A

    Article  Google Scholar 

  66. Katz SD (2003) Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. Congest Heart Fail 9: 9–15

    Article  PubMed  CAS  Google Scholar 

  67. Lichtenstein JR (2003) Use of sildenafil citrate in Raynaud’s phenomenon: comment on the article by Thompson et al. Arthritis Rheum 48: 282–283

    Article  PubMed  Google Scholar 

  68. Francis SH, Turko IV, Corbin JD (2001) Cyclic nucleotide phosphodiesterases: relating structure and function. Prog Nucleic Acid Res Mol Bio 65: 1–52

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Viagra Medical Strategies, Pfizer Ltd, Ramsgate Road, Bldg. 500, IPC 475, Sandwich, Kent, CT13 9NJ, UK

    Ian H. Osterloh

Authors
  1. Ian H. Osterloh
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. J.-W.-G.-University, Zeil 65-69, Frankfurt/Main, 60313, Germany

    Udo Dunzendorfer

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Basel AG

About this chapter

Cite this chapter

Osterloh, I.H. (2004). The discovery and development of Viagra® (sildenafil citrate). In: Dunzendorfer, U. (eds) Sildenafil. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7945-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7945-3_1

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9631-3

  • Online ISBN: 978-3-0348-7945-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation