Treatment of erectile dysfunction and lower urinary tract symptoms by phosphodiesterase inhibitors

Handbook of Experimental Pharmacology

Volumn 204, Issue , 2011, Pages 307-322

  Ückert, Stefan ^a,b   Stief, Christian G ^c  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b Urological Research Unit   (Germany)

^c LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

Author keywords

Lower urinary tract symptoms; Male erectile dysfunction; Oral pharmacotherapy; Phosphodiesterase (PDE) inhibitors

Indexed keywords

ADENYLATE CYCLASE; ADRENERGIC RECEPTOR BLOCKING AGENT; ALFUSOZIN; ALPHA ADRENERGIC RECEPTOR BLOCKING AGENT; APOMORPHINE; AVANAFIL; CHOLINERGIC RECEPTOR BLOCKING AGENT; DARIFENACIN; DOXAZOSIN; DUTASTERIDE; FESOTERODINE; FINASTERIDE; FORSKOLIN; LODENAFIL; NITRATE; OXYBUTYNIN; PHOSPHODIESTERASE IV INHIBITOR; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTAGLANDIN E1; SILDENAFIL; TADALAFIL; TAMSULOSIN; TESTOSTERONE; TOLTERODINE; UDENAFIL; UNCLASSIFIED DRUG; VARDENAFIL; VASOACTIVE INTESTINAL POLYPEPTIDE; VINPOCETINE; PHOSPHODIESTERASE INHIBITOR;

BENIGN PROSTATIC SYNDROME; BINDING AFFINITY; COLOR VISION DEFECT; COMBINATION CHEMOTHERAPY; DIABETES MELLITUS; DISEASE ASSOCIATION; DRUG ACTIVITY; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG POTENCY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; DYSPEPSIA; ERECTILE DYSFUNCTION; FLUSHING; HUMAN; HYPERCHOLESTEROLEMIA; HYPOGONADISM; LOWER URINARY TRACT SYMPTOM; MONOTHERAPY; NONHUMAN; NOSE CONGESTION; OUTCOME ASSESSMENT; OVERACTIVE BLADDER; PENIS ERECTION; PRIORITY JOURNAL; PROSTATE DISEASE; QUALITY OF LIFE; REVIEW; RHINITIS; SIDE EFFECT; SINGLE DRUG DOSE; SYSTEMATIC REVIEW; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; URGE INCONTINENCE; URINARY TRACT OBSTRUCTION; URINARY URGENCY; UROLITHIASIS; MALE; URINARY TRACT DISEASE;

ERECTILE DYSFUNCTION; HUMANS; MALE; PHOSPHODIESTERASE 5 INHIBITORS; PHOSPHODIESTERASE INHIBITORS; PROSTATIC DISEASES; URINARY BLADDER, OVERACTIVE; URINARY CALCULI; UROLOGIC DISEASES;

EID: 79960902595     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-17969-3_13     Document Type: Review

References (73)

1. Andersen JT, Ekman P, Wolf H, Beisland HO, Johansson JE, Kontturi M, Lehtonen T, Tveter K (1995) Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. Urology 46:631-637
2. Andersson KE (2008) How many drugs for LUTS due to BPH are too many? J Urol 180: 811-812
3. Andersson KE, Chapple C, Wein A (2001) The basis for drug treament of the overactive bladder. World J Urol 19:294-298 (Pubitemid 33777073)
4. Antoni FA (2000) Molecular diversity of cAMP signaling. Front Neuroendocrinol 21:103-132
5. Becker AJ, Stief CG, Meyer M, Truss MC, Forssmann WG, Jonas U (1998) The effect of the specific phosphodiesterase 4 inhibitor rolipram on the ureteral peristalsis in vitro and in vivo. J Urol 160:920-925 (Pubitemid 29479555)
6. Cahn D, Melman A, Valcic M, Christ GJ (1997) Forskolin: a promising new adjunct to intracavernous pharmacotherapy. J Urol 155:1789-1794 (Pubitemid 26127002)
7. Chiricos TN, Sanford E (1996) Cost consequences of surveillance, medical management or surgery for benign prostatic hyperplasia. J Urol 155:1311-1316 (Pubitemid 26081227)
8. Conti M, Jin SL (1999) The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 63:1-38
9. Eardly I, Cartledge J (2002) Tadalafil (CIALIS) for men with erectile dysfunction. Int J Clin Pract 56:300-304 (Pubitemid 34625031)
10. Emmick JT, Stuewe SR, MitchellM(2002) Overview of the cardiovascular effects of tadalafil. Eur Heart J 4(suppl H):H32-H47 (Pubitemid 35396802)
11. Essayan DM (2001) Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 108:671-680 (Pubitemid 33096193)
12. Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, Hetman J, Beavo JA, Philips SC (2000) Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Proc Natl Acad Sci USA 97:3702-3707 (Pubitemid 30183366)
13. Fink HA, McDonald 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 (Pubitemid 34655194)
14. Fisher AD, Smith JF, Pillar JS, St Denis S, Cheng JB (1998a) Isolation and characterization of PDE8A, a novel cAMP-specific phosphodiesterase. Biochem Biophys Res Commun 246:570-577 (Pubitemid 28420898)
15. Fisher AD, Smith JF, Pillar JS, St Denis S, Cheng JB (1998b) Isolation and characterization of PDE9A, a novel cGMP-specific phosphodiesterase. J Biol Chem 273:15559-15564 (Pubitemid 28298168)
16. Gacci M, del Popolo G, Macchiarella A, Celso M, Vittori G, Lapini A, Serni S, Sandner P, Maggi M, Carini M (2007) Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study. J Urol 178:2040-2043
17. Glina S, Toscano I, Gomatzky C, de Goes PM, Junior AN, Claro JF, Pagani E (2009) Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: a phase II clinical trial. J Sex Med 6:553-557
18. Gratzke C, Ückert S, Kedia G, Reich O, Schlenker B, Seitz M, Becker AJ, Stief CG (2007) In vitro effects of PDE5 inhibitors sildenafil, vardenafil and tadalafil on isolated human ureteral smooth muscle: a basic research approach. Urol Res 35:49-54
19. Greco EA, Spera G, Aversa A (2006) Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur Urol 50:940-947 (Pubitemid 44486492)
20. Guay D, Hamel P, Blouin M, Brideau C, Chan CC, Chauret N, Ducharme Y, Huang Z, Girard M, Jones TR, Laliberte F, Masson P, McAuliffe M, Piechuta H, Silva J, Young RN, Girard Y (2002) Discovery of L-791.943: a potent, selective, non-emetic and orally active phosphodiesterase 4 inhibitor. Bioorg Med Chem Lett 12:1457-1461 (Pubitemid 34521912)
21. Guess HA (1995) Epidemiology and natural history of benign prostatic hyperplasia. Urol Clin North Am 22:247-261
22. GÜlcer C, TÜzel E, Dogantekin E, Kiziltepe G (2008) Does sildenafil affect uroflowmetry values in men with lower urinary tract symptoms suggestive of benign prostatic enlargement? Urol Int 80:181-185 (Pubitemid 351440514)
23. Gur S, Sikka SC, Hellstrom WJ (2008) Novel phosphodiesterase 5 (PDE5) inhibitors in the alleviation of erectile dysfunction due to diabetes and ageing-induced oxidative stress. Expert Opin Investig Drugs 17:855-864 (Pubitemid 351864323)
24. Gutierrez P, Hernandez P, MasM(2005) Combining programmed intracavernous PGE1 injections and sildenafil on demand to salvage sildenafil non-responders. Int J Impot Res 17:354-358 (Pubitemid 41025769)
25. Han P, Zhu X, Michaeli T (1997) Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A) mRNA in human skeletal muscle and heart. J Biol Chem 272:16152-16157 (Pubitemid 27276430)
26. Hatzimouratidis K, Hatzichristou DG (2008) Looking to the future for erectile dysfunction therapies. Drugs 68:231-250
27. Heaton JP, Morales A, Owen J (1990) Topical glyceryltrinitrate causes measurable penile arterial dilatation in impotent men. J Urol 143:729-731 (Pubitemid 20112091)
28. Hieble JR, Ruffolo RR Jr (1996) The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hyperplasia: an overview. Pharmacol Res 33:145-160 (Pubitemid 26300700)
29. Holmquist F, Stief CG, Jonas U, Andersson KE (1991) Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit. Acta Physiol Scand 143:299-304
30. Jacobsen SJ, Guess HA, Panser L, Girman CJ, Chute CG, Oesterling JE, Lieber MM (1993) A population-based study of health care-seeking behaviour for treatment of urinary symptoms. Arch Fam Med 2:729-735
31. Kalsi JS, Kell PD (2004) Update on the oral treatments for male erectile dysfunction. J Eur Acad Dermatol Venereol 18:267-274 (Pubitemid 38618320)
32. Kang KK, Yu JY, Yoo M, Kwon JW (2005) The effect of DA-8159, a novel PDE5 inhibitor, on erectile function in the rat model of hypercholesterolemic erectile dysfunction. Int J Impot Res 17:409-416 (Pubitemid 43093241)
33. Kaplan SA, Gonzalez RR, Te AE (2007) Combination of alfuzosin and sildenafil is superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. Eur Urol 51:1717-1723 (Pubitemid 46634750)
34. KÜhn R, Ückert S, Stief CG, Truss MC, Lietz B, Bischoff E, Schramm M, Jonas U (2000) Relaxation of human ureteral smooth muscle in vitro by modulation of cyclic nucleotide dependent pathways. Urol Res 28:110-115 (Pubitemid 30397413)
35. KÜthe A, Magert HJ, Ückert S, Forssmann WG, Stief CG, Jonas U (2000) Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis. Eur Urol 38:108-114 (Pubitemid 30418026)
36. KÜthe A, Wiedenroth A, Magert HJ, Ückert S, Forssmann WG, Stief CG, Jonas U (2001) Expression of different phosphodiesterase genes in human cavernous smooth muscle. J Urol 165:280-283
37. Liguori G, Trombetta C, de Giorgi G, Pomara G, Maio G, Vecchio D, Ocello G, Ollandini G, Bucci S, Belgrano E (2009) Efficacy and safety of combined oral therapy with tadalafil and alfuzosin: an integrated approach to the management of patients with lower urinary tract symptoms and erectile dysfunction. Preliminary report. J Sex Med 6:544-552
38. Loughney K, Snyder PB, Uher L, Rosman GJ, Ferguson K, Florio VA (1999) Isolation and characterization of PDE10A, a novel human 3′.5′-cyclic nucleotide phosphodiesterase. Gene 234:109-117 (Pubitemid 29294097)
39. Lucas KA, Pitari GM, Kazerounian S, Ruiz-Stewart I, Park J, Schulz S, Chepenik KP, Waldman SA (2000) Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 52:375-414
40. Maurice DH, Palmer D, Tilley DG, Dunkerley HA, Netherton SJ, Raymond DR, Elbatany HS, Jimmo SL (2003) Cyclic nucleotide phosphodiesterase activity, expression, and targeting cells in the cardiovascular system. Mol Pharmacol 64:533-546 (Pubitemid 37048555)
41. Mazzu A, Nicholls A, ZinnyM(2001) Vardenafil: a new highly selective PDE5 inhibitor, interacts minimally with nitroglycerin in healthy middle-aged subjects. Int J Impot Res 13(suppl 5):S64 (Abstract
42. McVary KT, Monnig W, Camps JL, Young JM, Tseng LJ, van den Ende G (2007a) Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. J Urol 177:1071-1077 (Pubitemid 46216352)
43. McVary KT, Roehrborn CG, Kaminetsky JC, Auerbach SM, Wachs B, Young JM, Esler A, Sides GD, Denes BS (2007b) Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 177:1401-1407 (Pubitemid 46435965)
44. Michaeli T, Bloom TJ, Martins T, Loughney K, Ferguson K, Riggs M, Rodgers L, Beavo JA, Wigler M (1994) Isolation and characterization of a previously undetected human cAMP phosphodiesterase by complementation of cAMP phosphodiesterase deficient Saccharomyces cerevisiae. J Biol Chem 268:12925-12932
45. Oger S, Behr-Roussel D, Gorny D, Denys P, Lebret T, Alexandre L, Giuliano F (2007) Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition. Eur Urol 51:772-780
46. Ottensen B, Wagner G, Virag R, Fahrenkrug J (1984) Penile erection: possible role for vasoactive intestinal polypeptide as a neurotransmitter. Br J Med 288:9-11 (Pubitemid 14123598)
47. Porst H (1996) The rationale for prostaglandin E1 in erectile failure: a survey of worldwide experience. J Urol 155:802-815 (Pubitemid 26052655)
48. Rajasekaran M, Sikka S, Hellstrom W, Doherty P (1998) Evidence for the presence of the type 4 phosphodiesterase in isolated human cavernosal smooth muscle cells. Int J Impot Res 10(suppl 3): S55 (Abstract
49. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ (1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to non-adrenergic, non-cholinergic neurotransmission. N Engl J Med 326:90-94
50. Roehrborn CG, Marks LS, Fenter T, Freedman S, Tuttle J, Gittleman M, Morril B, Wolford ET (2004) Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 63:709-715 (Pubitemid 38479415)
51. Rybulkin SD, Yan C, Bornfeld KE, Beavo JA (2003) Cyclic GMP phosphodiesterase and smooth muscle function. Circ Res 93:280-291 (Pubitemid 37048240)
52. Saighi D, Zerbib M, Thiounn N, Flam T, Conquy S, Jacob L, dallAva-Santucci J, Debré B, Dinh-Xuan AT (2000) In vitro study of the modulation of human ureteral tonus by nitric oxide and zaprinast, a phosphodiesterase inhibitor. Prog Urol 10:1161-1168
53. Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC (2002) Sildenafil influences lower urinary tract symptoms. BJU Int 90:836-839 (Pubitemid 36693615)
54. Silver PJ, Dundore RL, Bode DC, de Garavilla L, Buchholz RA, van Aller G, Hamel LT, Bacon E, Singh B, Lesher GY (1997) Cyclic GMP potentiation by WIN 58237, a novel cyclic nucleotide phosphodiesterase inhibitor. J Pharmacol Exp Ther 271:1143-1149 (Pubitemid 24382614)
55. Smet PJ, Edyvane KA, Jonasvicius J, Marshall VR (1994) Colocalisation of nitric oxide synthase with vasoactive intestinal peptide, neuropeptide Y and thyrosine hydroxylase in nerves supplying the human ureter. J Urol 152:1292-1296 (Pubitemid 2141160)
56. Sommer F, Engelmann U (2004) Future options for combination therapy in the management of erectile dysfunction in older men. Drugs Aging 21:555-564 (Pubitemid 39070991)
57. Stief C, Porst H, Saenz de Tejada I, Ulbrich E, Beneke M, Vardenafil Study Group (2004) Sustained efficacy and tolerability with vardenafil over two years of treatment in men with erectile dysfunction. Int J Clin Pract 58:230-239 (Pubitemid 38559518)
58. Stief CG, Ückert S, Truss MC, Becker AJ, Machtens S, Jonas U (1996) A possible role for nitric oxide in the regulation of human ureteral smooth muscle tone in vitro. Urol Res 24:333-337 (Pubitemid 27022450)
59. Stief CG, Ückert S, Becker AJ, Truss MC, Jonas U (1998) Effects of specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. J Urol 159:1390-1393 (Pubitemid 28172841)
60. Stief CG, Porst H, Neuser D, Beneke M, Ulbrich E (2008) A randomised, placebo-controlled study to assess the efficacy of twice-daily vardenafil in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. Eur Urol 53:1236-1244
61. Taher A, Schulz-Knappe P, Meyer M, Truss MC, Forssmann WG, Stief CG, Jonas U (1994) Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro. World J Urol 12:286-291
62. Taher A, Meyer M, Stief CG, Jonas U, Forssmann WG (1997) Cyclic nucleotide phosphodiesterase isoenzymes in human cavernous smooth muscle. World J Urol 15:32-35 (Pubitemid 127769833)
63. Thadani U, Mazzu A (2002) Exercise-induced ischemia was not adversely affected by vardenafil during exercise stress test in men with coronary artery disease. Eur Urol 1(suppl 1):151 (Abstract
64. Toque HA, Teixeira CE, Lorenzetti R, Okuyama CE, Antunes E, de Nucci G (2008) Pharmacological characterization of a novel phosphodiesterase type 5 (PDE5) inhibitor, lodenafil carbonate, on human and rabbit corpus cavernosum. Eur J Pharmacol 591:189-195
65. Truss MC, Becker AJ, Djamillian MH, Stief CG, Jonas U (1994) Role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the diagnosis and treatment of erectile dysfunction. Urology 44:553-556
66. Truss MC, Ückert S, Stief CG, Kuczyk MA, Jonas U (1996a) Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle: I. Identification and characterization. Urol Res 24:123-128 (Pubitemid 26226247)
67. Truss MC, Ückert S, Stief CG, Kuczyk MA, Jonas U (1996b) Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle: II. Effect of various PDE-inhibitors on smooth muscle tone and cyclic nucleotide levels in vitro. Urol Res 24:129-134 (Pubitemid 26226248)
68. Truss MC, Stief CG, Ückert S, Becker AJ, Wefer J, Schultheiss D, Jonas U (2001) Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside. World J Urol 19:344-350 (Pubitemid 33777080)
69. Ückert S, Sandner P, Sigl K, Ulbrich E, Stief CG, Kuczyk MA (2009) Is there a role of the phosphodiesterase type 5 (PDE5) in the control of detrusor smooth muscle? A functional and molecular biology study. J Urol 181(suppl 4):152 (Abstract
70. Ückert S, KÜthe A, Stief CG, Jonas U (2001a) Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male erectile dysfunction. World J Urol 19:14-22
71. Ückert S, KÜthe A, Jonas U, Stief CG (2001b) Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol 166:2484-2490 (Pubitemid 33065340)
72. Ückert S, Hedlund P, Waldkirch E, Sohn M, Jonas U, Andersson KE, Stief CG (2004) Interactions between cGMP-and cAMP-pathways are involved in the regulation of penile smooth muscle tone. World J Urol 22:261-266 (Pubitemid 41406546)
73. Ückert S, Oelke M, Stief CG, Andersson KE, Jonas U, Hedlund P (2006) Immunohistochemical distribution of cAMP-and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate. Eur Urol 49:740-745 (Pubitemid 43374744)