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


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 microg) 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 microg) 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 microM) 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.
Streng
Tomi
T
Department of Clinical and Experimental Pharmacology, Lund University Hospital, Lund, Sweden.
Christoph
Thomas
T
Andersson
Karl-Erik
KE
D000818:Animals; D002219:Carbamates / Q000008:administration & dosage / Q000494:pharmacology*; D003243:Consciousness; D005260:Female; D009068:Movement; D010655:Phenylenediamines / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014563:Urodynamics / Q000187:drug effects*
D002219:Carbamates; D010655:Phenylenediamines; D015221:Potassium Channels; C101866:ezogabine