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Therapie der erektilen Dysfunktion im Jahr 2005

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Zusammenfassung

In der Therapie der erektilen Dysfunktion (ED) der nächsten 3–5 Jahre werden weiterhin Substanzen dominieren, welche den Arginin-NO-Guanylatzyklase-cGMP-PDE-5-Mechanismus attackieren und somit die intrazelluläre cGMP-Konzentration erhöhen. Viel versprechende Alternativen zu den PDE-5-Inhibitoren stellen Guanylatzyklase Aktivatoren und Rho-Kinase Inhibitoren dar, evtl. im Dualprinzip mit einem PDE-5-Inhibitor. Vom zentralen Ansatzpunkt her erscheint die intranasale Anwendung des Melanocortin-Agonisten PT-141 (Melanotan II) erfolgversprechend.

Da von den meisten Paaren eine Terminierung sexueller Aktivitäten nicht gewünscht ist, wird die zukünftige ED-Therapie hin zu Substanzen mit klinischer Wirksamkeit über 1–2 Tage oder aber zur täglich nächtlichen Anwendung niedrig dosierter Substanzen gehen, welche zur nächtlichen Reoxygenierung der Schwellkörper und damit einer Funktionsverbesserung führen. Die damit einhergehende Erhöhung der cGMP-Spiegel und Verbesserung der Endothelfunktion verspricht auch Benefite bei weiteren kardiovaskulären Erkrankungen und bei LUTS.

Abstract

Erectile dysfunction (ED) management in the following 3–5 years will be dominated by substances targeting the L-arginine-NO-guanylate cyclase-cGMP-PDE-5 pathway, resulting in an intracellular elevation of the cGMP concentrations. Promising alternatives to the PDE-5 inhibitors, such as guanylate cyclase activators and Rho-kinase inhibitors, may also effectively compliment a PDE-5 inhibitor. Intranasal application of the melanocortin agonist PT 141 (Melanotan II) seems to be promising.

As scheduled sexual activities are not preferred by the majority of couples, the future of ED-therapy will focus on drugs with a 1–2 day long efficacy window, or a daily bedtime application of low dosage agents which result in nocturnal reoxygenation of the cavernous bodies and in turn in functional improvement. Elevation of the cGMP levels and improvement of endothelial function as a result of this approach also promises benefits in cardiovascular diseases and in LUTS.

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Literatur

  1. Bahng MY, Kang KK, Ahn BO, Shim HJ, Kim SH,Yoo M, Kim WB, Jang IJ, Paick JS (2002) Tolerance and pharmacokinetics of single-dose DA-8159, a selective PDE 5 inhibitor, in healthy males. Int J Impotence Res 14 [Suppl 3]: S 101

  2. Bivalacqua TJ, Champion HC, Kadowitz PJ, Hellstrom WJG (2000) Effect of diabetes and Peyronie's disease on Nitric oxide synthase and arginase protein expression in human corpus cavernosum. Int J Impotence Res 38: p 83

    Google Scholar 

  3. Bischoff E, Schramm M, Straub A, Feurer A, Stasch J-P (2002) BAY 41–2272 a stimulator of soluble guanylyl cyclase induces NO-dependent penile erection in vivo. Int J Imptence Res 14 [Suppl 3]: S 43

    Google Scholar 

  4. Brioni JD, Nakane M, Hsieh GC, Moreland RB, Kolasa T, Sullivan JP (2002) Activators of soluble guanylate cyclase for the treatment of male erectile dysfunction. Int J Impotence Res 14: 8–14

    Article  CAS  Google Scholar 

  5. Chang S, Hypolite JA, Changolkar A, Wein AJ, Chacko SJ, Disanto ME (2002) Diabetes associated erectile dysfunction: Role of endothelin and Rho-kinase. J Urol 167 No 4 Suppl 237: 932

  6. Chitaley K, Webb RC, Mills TM (2003) The ups and downs of Rho-kinase and penile erection: upstream regulators and downstream substrates of Rho-kinase and their potential role in the erectile response. Int J Impotence Res 15: 105–109

    Article  CAS  Google Scholar 

  7. Christ GJ (2003) Editorial: Membrane bound guanylyl cyclase as a potential molecular target for the treatment of erectile dysfunction. J Urol 169: 1923

    PubMed  Google Scholar 

  8. Diamond LE, Earle DC, Shadiack A, Rosen RC, Molinoff P (2002) An evaluation of the safety and efficacy of intranasally administered PT-141. Int J Impotence Res 14 [Suppl 3]: S 20

    Google Scholar 

  9. El-Galley R, Rutland H, Talic R, Keane T, Clark H (2001) Long-term efficacy of sildenafil and tachyphylaxis effect. J Urol 166: 927–931

    PubMed  Google Scholar 

  10. Jackson G (2003) Editorial. PDE 5 Inhibitors: looking beyond. IJCP 57: 159

    PubMed  Google Scholar 

  11. 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

    CAS  PubMed  Google Scholar 

  12. Kang KK, Kohl SB, Ahn KJ, Ahn BO, Kim WB, Cho HK, Dong A (2002) Effect of DA-8159, a selective PDE-5 inhibitor on electroretinogram and retinal histopathology in rabbits. Int J Impotence Res 14 [Suppl 3]: S 44

  13. Kalsi JS, Rees RW, Hobbs AJ, Royle M, Kell PD, Ralph DJ, Moncada S, Cellek S (2003) Bay 41-2272, a novel nitric oxide independent soluble guanylate cyclase activator,relaxes human and rabbit corpus cavernosum in vitro. J Urol 169: 761–766

    CAS  PubMed  Google Scholar 

  14. Kwon TG, Yoo JJ, Atala A (2002): Penile corpora cavernosa replacement using tissue engineering techniques. J Urol 167 [Suppl]: 149

  15. Küthe A, Reinecke M, Ückert S, Becker A, David I, Heitland A, Stief CG, Forssman W-G, Mägert H-J (2003) Expression of guanylyl cyclase B in the human corpus cavernosum penis and the possible involvement of its ligand C-type natriuretic polypeptide in the induction of penile erection. J Urol 169: 1911–1917

    PubMed  Google Scholar 

  16. Maas R, Schwedhelm E, Albsmeier J, Böger RH (2002) The pathophysiology of erectile dysfunction related to endothelial dysfunction and mediators of vascular function. Vasc Med 7: 213–215

    Article  PubMed  Google Scholar 

  17. Madeo B, Fabbi F, Rochira V, Granata ARM, Valasi E, Balestrieri A (2002) Effects of sildenafil on sleep-related erection in healthy men. Int J Impotence Res 14 [Suppl 4]: S 45

    Google Scholar 

  18. Nakane M, Hsieh G, Miller LN, Chang R, Terranova MA, Moreland RB, Kolasa T, Brioni JD (2002) Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum tissue: synergism of nitric oxide and YC-1. Int J Impotence Res 14: 121–127

    Article  CAS  Google Scholar 

  19. Ozkara H, Bulent DR, Akkus E, Suleyman A (2002) The effect of sildenafil citrate on nocturnal penile tumescence. Int J Impotence Res 14 [Suppl 3]: S 67

    Google Scholar 

  20. Padma-Nathan H, Steidle C, Salem S, Tayse N, Yeager J, Harning R (2003) The efficacy and safety of a topical alprostadil cream, Alprox-TD, for the treatment of erectile dysfunction: two phase 2 studies in mild to moderate and severe ED. Int J Impotence Res 15: 10–17

    Article  CAS  Google Scholar 

  21. Porst H, Rosen R, Padma-Nathan H, Goldstein I, Giuliano F, Ulbrich E, Bandel T and the Vardenafil Study Group (2001) The efficacy and tolerability of vardenafil, a new oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial. Int J impotence Res 13: 192–199

    Article  CAS  Google Scholar 

  22. Porst H (2002) IC 351 (Tadalfil-Cialis®): update on clinical experience. Int J Impotence Res 14 [Suppl 1]: 57–64

    Google Scholar 

  23. Porst H, Padma-Nathan H, Giuliano F, Anglin G, Varanese L, Rosen R (2003) Efficacy of Tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology 62: 121–125

    Google Scholar 

  24. Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC (2002) Sildenafil influences lower urinary tract symptoms. BJU Intern 90: 836–839

    Article  CAS  PubMed  Google Scholar 

  25. Salonia A, Barbieri L, Deho F, Scapaticci E, Montorsi F (2002) Bed-time apomorphine and sildenafil: Results of a placebo-controlled Rigiscan study in healthy potent volunteers. Int J Impotence Res 14 [Suppl 4]: S 57

    Google Scholar 

  26. Sjunnesson J, Hedlund P, Mizusawa H, Andersson K-E (2002) Inhibition of Rho-associated kinases by Y-27632 produces erectile responses in the mouse. J Urol 167 [Suppl]: 238

  27. Souverein PC, Egberts ACG, Meuleman EJH, Urquhart J, Leufkens HGM (2002) Incidence and determinants of sildenafil discontinuation: the Dutch cohort of sildenafil users. Int J Impotence Res 14: 259–265

    Article  CAS  Google Scholar 

  28. Wessels H, Levine N, Hadley ME, Dorr R, Hruby V (2000) Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II. Int J Impotence Res 12 [Suppl 4]: S 74–79

  29. Wilkes N, White S, Cosgrove DJ, Rajasekaran M (2002) Y-27632, an inhibitor of Rho-kinase, improves erectile response in male hypertensive rats. J Urol 167 [Suppl]: 238

  30. Wilkes N, White S, Rajasekaran M (2003) PDE-V inhibitors synergizes Rho-kinase antagonism and enhances erectile response in male hypertensive rats. J Urol 169 [Suppl]: 360

  31. Yaman Ö, Tokath Z, Inal T, Anafarta K (2003) Effect of sildenafil on nocturnal erections of potent men. Int J Impotence Res 15: 117–121

    CAS  Google Scholar 

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  1. H. Porst, Hamburg

    H. Porst

  2. H. Porst, Neuer Jungfernstieg 6a, 20354, Hamburg

    H. Porst

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Porst, H. Therapie der erektilen Dysfunktion im Jahr 2005. Urologe [A] 42, 1330–1336 (2003). https://doi.org/10.1007/s00120-003-0418-0

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