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Urodynamic effects of the K+ channel (KCNQ) opener retigabine in freely moving, conscious rats.

Streng, Tomi LU ; Christoph, Thomas and Andersson, Karl-Erik LU (2004) In Journal of Urology 172(5 Pt 1). p.2054-2058
Abstract
Purpose: Retigabine is a novel anticonvulsant drug that not only augments gamma-aminobutyric acid mechanisms, but also opens voltage gated K+ channels (KCNQ). In this study we investigated the effects of retigabine on detrusor activity in rats. Materials and Methods: To conscious, female Sprague-Dawley rats undergoing continuous cystometry retigabine was given intravenously (0.5, 1 and 5 mg/kg(-1)). The KCNQ channel blocker linopirdine was given intravenously (2 mg/kg(-1)) 5 minutes prior to retigabine (1 mg/kg(-1)). In addition, retigabine was given intracerebroventricularly (1, 5 and 10 mug) and intravesically (100, 500 and 1,000 ng ml(-1)). The effects of the drug (intravesical administration) on capsaicin induced bladder overactivity... (More)
Purpose: Retigabine is a novel anticonvulsant drug that not only augments gamma-aminobutyric acid mechanisms, but also opens voltage gated K+ channels (KCNQ). In this study we investigated the effects of retigabine on detrusor activity in rats. Materials and Methods: To conscious, female Sprague-Dawley rats undergoing continuous cystometry retigabine was given intravenously (0.5, 1 and 5 mg/kg(-1)). The KCNQ channel blocker linopirdine was given intravenously (2 mg/kg(-1)) 5 minutes prior to retigabine (1 mg/kg(-1)). In addition, retigabine was given intracerebroventricularly (1, 5 and 10 mug) and intravesically (100, 500 and 1,000 ng ml(-1)). The effects of the drug (intravesical administration) on capsaicin induced bladder overactivity were also tested. Results: Retigabine given intravenously (1 mg/kg(-1)) decreased baseline and maximal bladder pressures, increased voided and infused volumes, and increased voiding intervals. Retigabine (10 mug) given intracerebroventricularly decreased baseline pressure and increased voided and infused volumes as well as voiding intervals. However, bladder pressures were not significantly affected. Intravesical retigabine (1,000 ng.ml(-1)) decreased maximal bladder pressure, increased voided and infused volumes, and increased voiding intervals. Given intravesically for 30 minutes prior to intravesical capsaicin (30 muM) instillation retigabine (1,000 ng.ml(-1)) decreased the detrusor overactivity induced by capsaicin. The KNCQ channel blocker linopirdine (2 mg/kg(-1)) completely blocked the effects of intravenous retigabine (1 mg/kg(-1)). Conclusions: Retigabine given intravenously, intracerebroventricularly and intravesically increased micturition volume and voiding intervals and, when given intravesically, it decreased capsaicin induced detrusor overactivity, suggesting that KCNQ channels can be interesting targets for drugs aiming at micturition control. Retigabine may be a candidate to test as a treatment for detrusor overactivity in humans. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
linopirdine, bladder, rats, urination, calcium channels, Sprague-Dawley
in
Journal of Urology
volume
172
issue
5 Pt 1
pages
2054 - 2058
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000224463600078
  • pmid:15540788
  • scopus:5444225675
ISSN
1527-3792
DOI
10.1097/01.ju.0000138155.33749.f4
language
English
LU publication?
yes
id
7e8fe12d-9218-4614-8db7-ecb9ac4f7216 (old id 130867)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15540788&dopt=Abstract
date added to LUP
2007-07-06 08:28:10
date last changed
2017-09-10 04:27:51
@article{7e8fe12d-9218-4614-8db7-ecb9ac4f7216,
  abstract     = {Purpose: Retigabine is a novel anticonvulsant drug that not only augments gamma-aminobutyric acid mechanisms, but also opens voltage gated K+ channels (KCNQ). In this study we investigated the effects of retigabine on detrusor activity in rats. Materials and Methods: To conscious, female Sprague-Dawley rats undergoing continuous cystometry retigabine was given intravenously (0.5, 1 and 5 mg/kg(-1)). The KCNQ channel blocker linopirdine was given intravenously (2 mg/kg(-1)) 5 minutes prior to retigabine (1 mg/kg(-1)). In addition, retigabine was given intracerebroventricularly (1, 5 and 10 mug) and intravesically (100, 500 and 1,000 ng ml(-1)). The effects of the drug (intravesical administration) on capsaicin induced bladder overactivity were also tested. Results: Retigabine given intravenously (1 mg/kg(-1)) decreased baseline and maximal bladder pressures, increased voided and infused volumes, and increased voiding intervals. Retigabine (10 mug) given intracerebroventricularly decreased baseline pressure and increased voided and infused volumes as well as voiding intervals. However, bladder pressures were not significantly affected. Intravesical retigabine (1,000 ng.ml(-1)) decreased maximal bladder pressure, increased voided and infused volumes, and increased voiding intervals. Given intravesically for 30 minutes prior to intravesical capsaicin (30 muM) instillation retigabine (1,000 ng.ml(-1)) decreased the detrusor overactivity induced by capsaicin. The KNCQ channel blocker linopirdine (2 mg/kg(-1)) completely blocked the effects of intravenous retigabine (1 mg/kg(-1)). Conclusions: Retigabine given intravenously, intracerebroventricularly and intravesically increased micturition volume and voiding intervals and, when given intravesically, it decreased capsaicin induced detrusor overactivity, suggesting that KCNQ channels can be interesting targets for drugs aiming at micturition control. Retigabine may be a candidate to test as a treatment for detrusor overactivity in humans.},
  author       = {Streng, Tomi and Christoph, Thomas and Andersson, Karl-Erik},
  issn         = {1527-3792},
  keyword      = {linopirdine,bladder,rats,urination,calcium channels,Sprague-Dawley},
  language     = {eng},
  number       = {5 Pt 1},
  pages        = {2054--2058},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Urodynamic effects of the K+ channel (KCNQ) opener retigabine in freely moving, conscious rats.},
  url          = {http://dx.doi.org/10.1097/01.ju.0000138155.33749.f4},
  volume       = {172},
  year         = {2004},
}