Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology:: Present and future

被引:89
作者
Ueckert, Stefan [1 ]
Hedlund, Petter
Andersson, Karl-Erik
Truss, Michael C.
Jonas, Udo
Stief, Christian G.
机构
[1] Hannover Med Sch, Dept Urol, D-30625 Hannover, Germany
[2] Univ Lund Hosp, Dept Clin Pharmacol, S-22185 Lund, Sweden
[3] Univ Munich, Dept Urol, Acad Hosp Grosshadern, Munich, Germany
[4] PharmaCeuticals GmbH, IPF, Urol Res Grp, Hannover, Germany
关键词
human urogenital tract; phosphodiesterase (PIDE) enzymes; phosphodiesterase inhibitors;
D O I
10.1016/j.eururo.2006.05.025
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Objectives & Methods: Diseases of the human urinary tract represent common morbidities characterized by a high prevalence in the population of most westernized countries. The existeince of a significant number of affected patients and the recent increase in scientific attention has resulted in various experimental and clinical efforts in order to evaluate the mechanisms controlling the function of urinary tract organs. This review attempts to describe the physiology and pharmacology of phosphodiesterase (PDE) isoenzymes with special regard to their (potential) use in disorders of the human urogenital tract. Results: The promising clinical data for the orally active phosphodiesterase (PDE) inhibitors sildenafil, vardenafil and tadalafil, used in the treatment of male erectile dysfunction (MED), has boosted research activities on the significance of the cyclic GMP- and cyclic AMP pathway in other genitourinary tract tissues, such as the bladder, prostate, ureter, urethra, as well as female genital tissues. Based on the more extensive understanding of the pathways controlling the function of the male and female urogenital tract, orally administered phosphodiesterase inhibitors are considered a logical and straightforward approach for treating urological diseases. Due to the unending charge to conceive advanced first-line treatments, new therapeutic options taking into consideration the cyclic nucleotide signaling have been introduced or might be launched in the near future. Upcoming strategies will not only focus on the nitric oxide (No)/cGMP cascade but also on compounds modulating signal transduction mediated by cyclic adenosine monophosphate, as well as combined agents in order to affect multiple peripheral intracellular targets. Conclusions: The article highlights cGMP- and cAMP-pathways, PDE subtypes and their present or putative future clinical significance in urological practice. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1194 / 1207
页数:14
相关论文
共 122 条
[1]   Phosphodiesterase 5 inhibitors in rapid ejaculation - Potential use and possible mechanisms of action [J].
Abdel-Hamid, IA .
DRUGS, 2004, 64 (01) :13-26
[2]   CAN FINASTERIDE REVERSE THE PROGRESS OF BENIGN PROSTATIC HYPERPLASIA - A 2-YEAR PLACEBO-CONTROLLED STUDY [J].
ANDERSEN, JT ;
EKMAN, P ;
WOLF, H ;
BEISLAND, HO ;
JOHANSSON, JE ;
KONTTURI, M ;
LEHTONEN, T ;
TVETER, K ;
BODKER, A ;
VEDEL, O ;
NORDLING, J ;
POULSEN, AL ;
SCHOU, J ;
HVIDT, V ;
HANSEN, JB ;
MEYHOFF, HH ;
ELDRUP, J ;
HARTWELL, D ;
COLSTRUP, H ;
LYNGDORF, P ;
NIELSEN, AH ;
LARSEN, E ;
WALTER, S ;
LARSEN, EH ;
THYBO, E ;
MOMMSEN, S ;
BROK, KE ;
PALM, L ;
GENSTER, H ;
ANDERSEN, M ;
KAUPPINEN, P ;
RAUVALA, M ;
HAKKINEN, J ;
TAMMELA, T ;
TAINIO, H ;
HYNNINEN, O ;
TIITINEN, J ;
LEHTORANTA, K ;
ALAOPAS, M ;
PERTTILA, I ;
PETAS, A ;
RINTALA, E ;
SALMINEN, R ;
JUUSELA, H ;
HANSSON, E ;
VONWENDT, R ;
TUHKANEN, K ;
TALJA, M ;
NURMI, M ;
PUNTALA, P .
UROLOGY, 1995, 46 (05) :631-637
[3]  
ANDERSON KE, 1993, PHARMACOL REV, V45, P253
[4]   The basis for drug treatment of the overactive bladder [J].
Andersson, KE ;
Chapple, C ;
Wein, A .
WORLD JOURNAL OF UROLOGY, 2001, 19 (05) :294-298
[5]   Molecular diversity of cyclic AMP signalling [J].
Antoni, FA .
FRONTIERS IN NEUROENDOCRINOLOGY, 2000, 21 (02) :103-132
[6]  
Bai Wen-Jun, 2002, Zhonghua Nan Ke Xue, V8, P88
[7]   TERMINAL NEUROENDOCRINE DIFFERENTIATION OF HUMAN PROSTATE CARCINOMA-CELLS IN RESPONSE TO INCREASED INTRACELLULAR CYCLIC-AMP [J].
BANG, YJ ;
PIRNIA, F ;
FANG, WG ;
KANG, WK ;
SARTOR, O ;
WHITESELL, L ;
HA, MJ ;
TSOKOS, M ;
SHEAHAN, MD ;
NGUYEN, P ;
NIKLINSKI, WT ;
MYERS, CE ;
TREPEL, JB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (12) :5330-5334
[8]   Sexual psychophysiology and effects of sildenafil citrate in oestrogenised women with acquired genital arousal disorder and impaired orgasm: a randomised controlled trial [J].
Basson, R ;
Brotto, LA .
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2003, 110 (11) :1014-1024
[9]   The effect of the specific phosphodiesterase-IV-inhibitor rolipram on the ureteral peristalsis of the rabbit in vitro and in vivo [J].
Becker, AJ ;
Stief, CG ;
Meyer, M ;
Truss, MC ;
Forssmann, WG ;
Jonas, U .
JOURNAL OF UROLOGY, 1998, 160 (03) :920-925
[10]   Safety and efficacy of sildenafil citrate for the treatment of female sexual arousal disorder: A double-blind, placebo controlled study [J].
Berman, JR ;
Berman, LA ;
Toler, SM ;
Gill, J ;
Haughie, S .
JOURNAL OF UROLOGY, 2003, 170 (06) :2333-2338