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

Ueckert, Stefan; Hedlund, Petter LU ; Andersson, Karl-Erik LU ; Truss, Michael C.; Jonas, Udo and Stief, Christian G. (2006) In European Urology 50(6). p.1194-1207
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
human urogenital tract, phosphodiesterase (PIDE) enzymes, phosphodiesterase inhibitors
in
European Urology
volume
50
issue
6
pages
1194 - 1207
publisher
Elsevier
external identifiers
  • wos:000242412200013
  • scopus:33750633515
ISSN
1873-7560
DOI
10.1016/j.eururo.2006.05.025
language
English
LU publication?
yes
id
e45b9f09-2d33-4876-aed6-406a3a82a5e7 (old id 685212)
date added to LUP
2008-01-04 15:49:36
date last changed
2019-11-13 03:28:08
@article{e45b9f09-2d33-4876-aed6-406a3a82a5e7,
  abstract     = {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.},
  author       = {Ueckert, Stefan and Hedlund, Petter and Andersson, Karl-Erik and Truss, Michael C. and Jonas, Udo and Stief, Christian G.},
  issn         = {1873-7560},
  keyword      = {human urogenital tract,phosphodiesterase (PIDE) enzymes,phosphodiesterase inhibitors},
  language     = {eng},
  number       = {6},
  pages        = {1194--1207},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: Present and future},
  url          = {http://dx.doi.org/10.1016/j.eururo.2006.05.025},
  volume       = {50},
  year         = {2006},
}