Phosphodiesterase (PDE) inhibitors in the treatment of lower urinary tract dysfunction

British Journal of Clinical Pharmacology

Volumn 72, Issue 2, 2011, Pages 197-204

  Ückert, Stefan ^a,b   Oelke, Matthias ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b Urological Research Unit   (Germany)

Author keywords

Benign prostatic hyperplasia (BPH); Lower urinary tract symptoms (LUTS); Overactive bladder (OAB); Pharmacotherapy; Phosphodiesterase inhibitors

Indexed keywords

1 (3 CHLOROANILINO) 4 PHENYLPHTHALAZINE; 1 [6 CHLORO 4 (3,4 METHYLENEDIOXYBENZYLAMINO) 2 QUINAZOLINYL] 4 PIPERIDINECARBOXYLIC ACID; 4 (3 BUTOXY 4 METHOXYBENZYL) 2 IMIDAZOLIDINONE; 5 (4 ACETAMIDOPHENYL) 2(1H) PYRAZINONE; AMRINONE; AVANAFIL; BAY 736691; CALMODULIN INHIBITOR; CILOMILAST; CILOSTAMIDE; DENBUFYLLINE; DIPYRIDAMOLE; ENOXIMONE; ETAZOLATE; LODENAFIL; MILRINONE; NITRAQUAZONE; PHOSPHODIESTERASE INHIBITOR; PICLAMILAST; QUAZINONE; ROFLUMILAST; ROLIPRAM; SCH 51866; SIGUAZODAN; SILDENAFIL; SILDENAFIL NITRATE; SULINDAC SULFONE; TA 1790; TADALAFIL; UDENAFIL; UNCLASSIFIED DRUG; UNINDEXED DRUG; VARDENAFIL; VINPOCETINE; ZAPRINAST; ZARDAVERINE; ZK 803616;

ARTERY THROMBOSIS; ASTHMA; BRAIN DYSFUNCTION; CHRONIC OBSTRUCTIVE LUNG DISEASE; COLITIS; COLON CANCER; DEMENTIA; DEPRESSION; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; ERECTILE DYSFUNCTION; HEART FAILURE; HUMAN; HYPERTENSION; INTERMITTENT CLAUDICATION; LOWER URINARY TRACT SYMPTOM; LUNG EMBOLISM; MONOTHERAPY; OUTCOME ASSESSMENT; OVERACTIVE BLADDER; PEYRONIE DISEASE; PREMATURE EJACULATION; PRIORITY JOURNAL; PROSTATE CARCINOMA; PROSTATE HYPERTROPHY; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RAYNAUD PHENOMENON; REVIEW; SINGLE DRUG DOSE; TREATMENT INDICATION; UROLITHIASIS;

HUMANS; LOWER URINARY TRACT SYMPTOMS; PHOSPHODIESTERASE INHIBITORS; URINARY TRACT; UROLOGIC DISEASES;

EID: 79960159705     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2010.03828.x     Document Type: Review

References (61)

1. Rybulkin SD, Yan C, Bornfeld KE, Beavo JA. Cyclic GMP phosphodiesterase and smooth muscle function. Circ Res 2003; 93: 280-91.
2. Maurice DH, Palmer D, Tilley DG, Dunkerley HA, Netherton SJ, Raymond DR, Elbatany HS, Jimmo SL. Cyclic nucleotide phosphodiesterase activity, expression, and targeting cells in the cardiovascular system. Mol Pharmacol 2003; 64: 533-46.
3. Conti M, Jin SL. The molecular biology of cyclic nucleotide phosphodiesterases. Prog Nucleic Acid Res Mol Biol 1999; 63: 1-38.
4. Essayan DM. Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 2001; 108: 671-80.
5. Gupta R, Kumar G, Kumar RS. An update on cyclic nucleotide phosphodiesterase (PDE) inhibitors: phosphodiesterases and drug selectivity. Methods Find Exp Clin Pharmacol 2005; 27: 101-8.
6. Ückert S, Küthe A, Stief CG, Jonas U. Phosphodiesterase isoenzymes as pharmacological targets in the treatment of male erectile dysfunction. World J Urol 2001; 19: 14-22.
7. Kalsi JS, Kell PD. Update on the oral treatments for male erectile dysfunction. J Eur Acad Dermatol Venereol 2004; 18: 267-74.
8. Ückert S, Küthe A, Jonas U, Stief CG. Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol 2001; 166: 2484-90.
9. Ückert S, Oelke M, Stief CG, Andersson KE, Jonas U, Hedlund P. Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate. Eur Urol 2006; 49: 740-5.
10. Ückert S, Sormes M, Kedia GT, Scheller F, Knapp WH, Jonas U, Stief CG. Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and accumulation of cyclic nucleotides in isolated human prostatic tissue. Urology 2008; 71: 526-30.
11. Kedia GT, Ückert S, Kedia M, Kuczyk MA. Effects of phosphodiesterase inhibitors on contraction induced by endothelin-1 of isolated human prostatic tissue. Urology 2009; 73: 1397-401.
12. Heuer O, Ückert S, Dobler G, Klocker H, Stief CG, Truss MC, Bartsch G, Jonas U. Effects of phosphodiesterase inhibitors and nitric oxide donors on cultured human prostatic smooth muscle cells. J Urol 2003; 169 (No 4, Suppl.): 286 (Abstract presented at the 98th Annual Meeting of the American Urological Association, Chicago, IL, USA, 26-April to 01-May-2003).
13. Guess HA. Epidemiology and natural history of benign prostatic hyperplasia. Urol Clin North Am 1995; 22: 247-61.
14. Jacobsen SJ, Guess HA, Panser L, Girman CJ, Chute CG, Oesterling JE, Lieber MM. A population-based study of health care-seeking behaviour for treatment of urinary symptoms. Arch Fam Med 1993; 2: 729-35.
15. Hieble JR, Ruffolo RR. The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hyperplasia: an overview. Pharmacol Res 1996; 33: 145-60.
16. Andersen JT, Ekman P, Wolf H, Beisland HO, Johansson JE, Kontturi M, Lehtonen T, Tveter K. Can finasteride reverse the progress of benign prostatic hyperplasia? A two-year placebo-controlled study. Urology 1995; 46: 631-7.
17. Roehrborn CG, Marks LS, Fenter T, Freedman S, Tuttle J, Gittleman M, Morril B, Wolford ET. Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia. Urology 2004; 63: 709-15.
18. Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC. Sildenafil influences lower urinary tract symptoms. BJU Int 2002; 90: 836-9.
19. Mulhall JP, Guhring P, Parker M, Hopps C. Assessment of the impact of sildenafil citrate on lower urinary tract symptoms in men with erectile dysfunction. J Sex Med 2006; 3: 662-7.
20. McVary KT, Monnig W, Camps JL, Young JM, Tseng LJ, van den Ende G. 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 2007; 177: 1071-7.
21. McVary KT, Roehrborn CG, Kaminetsky JC, Auerbach SM, Wachs B, Young JM, Esler A, Sides GD, Denes BS. Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2007; 177: 1401-7.
22. Roehrborn CG, McVary KT, Elion-Mboussa A, Viktrup L. Tadalafil administered once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a dose finding study. J Urol 2008; 180: 1228-34.
23. Porst H, McVary KT, Montorsi F, Sutherland P, Elion-Mboussa A, Wolka AM, Viktrup L. Effects of once-daily tadalafil on erectile function in men with erectile dysfunction and signs and symptoms of benign prostatic hyperplasia. Eur Urol 2009; 56: 727-35.
24. Stief CG, Porst H, Neuser D, Beneke M, Ulbrich E. 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 2008; 53: 1236-44.
25. Kaplan SA, Gonzalez RR, Te AE. Combination of alfuzosin and sildenafil is superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. Eur Urol 2007; 51: 1717-23.
26. Liguori G, Trombetta C, de Giorgi G, Pomara G, Maio G, Vecchio D, Ocello G, Ollandini G, Bucci S, Belgrano E. 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 2009; 6: 544-52.
27. Bechara A, Romano S, Casabé A, Haime S, Dedola P, Hernández C, Rey H. Comparative efficacy assessment of tamsulosin vs. tamsulosin plus tadalafil in the treatment of LUTS/BPH. Pilot study. J Sex Med 2008; 5: 2170-8.
28. Chung BH, Lee JY, Lee SH, Yoo SJ, Lee SW, Oh CY. Safety and efficacy of the simultaneous administration of udenafil and an alpha-blocker in men with erectile dysfunction concomitant with BPH/LUTS. Int J Impot Res 2009; 21: 122-8.
29. Tuncel A, Nalcacioglu V, Ener K, Aslan Y, Aydin O, Atan A. Sildenafil citrate and tamsulosin combination is not superior to monotherapy in treating lower urinary tract symptoms and erectile dysfunction. World J Urol 2010; 28: 17-22.
30. Roehrborn CG, Kaminetsky JC, Auerbach SM, Montelongo RM, Elion-Mboussa A, Viktrup L. Changes in peak urinary flow and voiding efficiency in men with signs and symptoms of benign prostatic hyperplasia during once daily tadalafil treatment. BJU Int 2009; 105: 502-7.
31. Dmochowski R, Roehrborn C, Klise S, Xu L, Kaminetsky J, Kraus S. Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. J Urol 2010; 183: 1092-7.
32. Gülcer C, Tüzel E, Dogantekin E, Kiziltepe G. Does sildenafil affect uroflowmetry values in men with lower urinary tract symptoms suggestive of benign prostatic enlargement? Urol Int 2008; 80: 181-5.
33. Guven EO, Balbay MD, Mete K, Serefoglu EC. Uroflowmetric assessment of acute effects of sildenafil on the voiding of men with erectile dysfunction and symptomatic benign prostatic hyperplasia. Int Urol Nephrol 2009; 41: 287-92.
34. Berger AP, Deibl M, Leonhartsberger N, Bektic J, Horninger W, Fritsche G, Steiner H, Pelzer AE, Bartsch G, Frauscher F. Vascular damage as a risk factor for benign prostatic hyperplasia and erectile dysfunction. BJU Int 2005; 96: 1073-8.
35. Berger AP, Horninger W, Bektic J, Pelzer A, Spranger R, Bartsch G, Frauscher F. Vascular resistance in the prostate evaluated by colour Doppler ultrasonography: is benign prostatic hyperplasia a vascular disease? BJU Int 2006; 98: 587-90.
36. Berger AP, Bartsch G, Deibl M, Alber H, Pachinger O, Fritsche G, Rantner B, Fraedrich G, Pallwein L, Aigner F, Horninger W, Frauscher F. Atherosclerosis as a risk factor for benign prostatic hyperplasia. BJU Int 2006; 98: 1038-42.
37. Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, Weinstein D. The effects of antimuscarinic treatments in overactive bladder: an update of a systematic review and meta-analysis. Eur Urol 2008; 54: 543-62.
38. Andersson KE. Treatment-resistant detrusor overactivity - underlying pharmacology and potential mechanisms. Int J Clin Pract 2006; 151 (Suppl): 8-16.
39. Andersson KE. Antimuscarinics for treatment of overactive bladder. Lancet Neurol 2004; 3: 46-53.
40. Andersson KE. Pharmacotherapy of the overactive bladder. Discov Med 2009; 8: 118-24.
41. Truss MC, Ückert S, Stief CG, Kuczyk MA, Jonas U. Cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human detrusor smooth muscle: I. Identification and characterization. Urol Res 1996; 24: 123-8.
42. Truss MC, Ückert S, Stief CG, Kuczyk MA, Jonas U. 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 1996; 24: 129-34.
43. Ückert S, Sandner P, Sigl K, Ulbrich E, Stief CG, Kuczyk MA. Is there a role for the phosphodiesterase type 5 (PDE5) in the control of detrusor smooth muscle? A functional and molecular biology study. J Urol 2009; 181 (No 4, Suppl.): 152 (Abstract, presented at the 104th Annual Meeting of the American Urological Association, Chicago, IL, USA, 25-April to 30-April-2009).
44. Oger S, Behr-Roussel D, Gorny D, Denys P, Lebret T, Alexandre L, Giuliano F. Relaxation of phasic contractile activity of human detrusor strips by cyclic nucleotide phosphodiesterase type 4 inhibition. Eur Urol 2007; 51: 772-80.
45. Bittencourt JA, Tano T, Gajar SA, Resende AC, de Lemos Neto M, Damião R, Criddle DN, de Bem GF, de Moura RS. Relaxant effects of sildenafil on the human isolated bladder neck. Urology 2009; 73: 427-30.
46. Oger S, Behr-Roussel D, Gorny D, Lebret T, Validire P, Cathelineau X, Alexandre L, Giuliano F. Signalling pathways involved in sildenafil-induced relaxation of human bladder dome smooth muscle. Br J Pharmacol 2010; 160: 1135-43.
47. Ückert S, Sigl K, Waldkirch E, Sandner P, Ulbrich E, Oelke M, Stief CG, Kuczyk MA. [Significance of phosphodiesterase isoenzymes in the control of human detrusor smooth muscle function: an immunohistochemical and functional study.]. Der Urologe 2009; 48: 764-9. (Article in German).
48. Filippi S, Morelli A, Sandner P, Fibbi B, Mancina R, Marini M, Gacci M, Vignozzi L, Vannelli GB, Carini M, Forti G, Maggi M. Characterization and functional role of androgen-dependent PDE5 activity in the bladder. Endocrinology 2007; 148: 1019-29.
49. Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, de Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 2010; 7: 59-69.
50. Beamon CR, Mazar C, Salkini MW, Phull HS, Comiter CV. The effect of sildenafil citrate on bladder outlet obstruction: a mouse model. BJU Int 2009; 104: 252-6.
51. Clark C, Kimm S, Phull HS, Tathireddy A, Comiter CV. Can sildenafil reverse the pathophysiologic changes of partial bladder outlet obstruction in a mouse model? J Urol 2010; 183 (No 4, Suppl.): 173 (Abstract presented at the 105th Annual Meeting of the American Urological Association, San Francisco, CA, USA, 28-May to 03-June-2010).
52. Lin AT, Chen KK, Yang CH, Chang LS. Effects of outlet obstruction and its reversal on mitochondrial enzyme activity in rabbit urinary bladders. J Urol 1998; 160 (Pt 1): 2258-62.
53. Hsu TH, Levin RM, Wein AJ, Haugaard N. Alterations of mitochondrial oxidative metabolism in rabbit urinary bladder after partial outlet obstruction. Mol Cell Biochem 1994; 141: 21-6.
54. Truss MC, Stief CG, Ückert S, Becker AJ, Schultheiss D, Machtens S, Jonas U. Initial clinical experience with the selective phosphodiesterase (PDE) 1 isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder. World J Urol 2000; 18: 439-43.
55. Gacci M, del Popolo G, Macchiarella A, Celso M, Vittori G, Lapini A, Serni S, Sandner P, Maggi M, Carini M. Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study. J Urol 2007; 178: 2040-3.
56. Gacci M, Ierardi A, Rose AD, Tazzioli S, Scapaticci E, Filippi S, Maggi M, Nicita G, Carini M, Montorsi F. Vardenafil can improve continence recovery after bilateral nerve sparing prostatectomy: results of a randomized, double blind, placebo-controlled pilot study. J Sex Med 2010; 7 (Pt 1): 234-43.
57. Nishiguchi J, Kwon DD, Kaiho Y, Chancellor MB, Kumon H, Snyder PB, Yoshimura N. Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor. BJU Int 2007; 99: 680-6.
58. Waldkirch E, Ückert S, Hedlund P, Kuczyk MA. Is there a functional significance of the cyclic AMP-mediated signalling in the control of the human prostate? Eur Urol 2008; 3 (No 10): 47 (Abstract presented at the 8th Central European Meeting of the European Association of Urology, Warsaw, Poland, 24-October and 25-October-2008).
59. Kedia G, Schönfeld DJ, Seidler M, Kuczyk MA, Ückert S. Evaluating the significance of the cyclic AMP-mediated signalling in the control of smooth muscle of the human prostate - a functional and biochemical study. J Urol 2010; 183 (No 4, Suppl.): 542 (Abstract presented at the 105th Annual Meeting of the American Urological Association, San Francisco, CA, USA, 29-May to 03-June-2010).
60. Waldkirch E, Ückert S, Sigl K, Langnaese K, Richter K, Stief CG, Kuczyk MA, Hedlund P. Expression of cAMP-dependent protein kinase isoforms in the human prostate: functional significance and relation to PDE4. Urology 2010; 76: 515.e8-14.
61. Bazrafshan S. Effekte selektiver Phosphodiesterase (PDE)-Inhibitoren auf die glatte Muskulatur der humanen Vesicula seminalis in vitro. Doctoral Thesis, Hannover Medical School, Division of Surgery, Hannover, Germany, 2007.