Alpha2-adrenoceptor blockade potentiates the effect of duloxetine on sneeze induced urethral continence reflex in rats.

The Journal of Urology
Takeya KittaNaoki Yoshimura

Abstract

Serotonin and norepinephrine reuptake inhibitors such as duloxetine have clinical efficacy for stress urinary incontinence. However, the therapeutic dose of duloxetine is often associated with unwanted side effects. We examined whether combined alpha(2)-adrenoceptor antagonists could decrease the duloxetine dose due to synergistic effects. We used normal female rats and rats with stress urinary incontinence induced by vaginal distention. Urethral responses were measured using a microtransducer tipped catheter. We evaluated the effect of low dose duloxetine (0.1 mg/kg), alpha(2)-adrenoceptor antagonists (idazoxan or yohimbine) and sequential administration of drugs on urethral pressure response amplitude during sneezing and urethral baseline pressure. Sneeze induced leak point pressure was also measured. In normal and vaginally distended rats low dose duloxetine did not alter urethral pressure response amplitude during sneezing but it significantly increased urethral baseline pressure. When low dose duloxetine was co-applied with alpha(2)-adrenoceptor antagonists, urethral pressure response amplitude during sneezing was significantly increased. In all 7 vaginally distended rats leakage was observed during sneezing. After low dos...Continue Reading

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Citations

Mar 13, 2013·Medical Science Monitor Basic Research·Ivan JandricPredrag Sikiric
Jun 11, 2011·Neurourology and Urodynamics·Hidehiro KakizakiNaoki Wada
Apr 7, 2018·Neurourology and Urodynamics·Mifuka OuchiNobuo Shinohara
Apr 3, 2019·Neurourology and Urodynamics·Mifuka OuchiNobuo Shinohara
Mar 13, 2012·International Journal of Urology : Official Journal of the Japanese Urological Association·Naoki Yoshimura, Minoru Miyazato
Nov 7, 2012·International Journal of Urology : Official Journal of the Japanese Urological Association·Yusuke KoikeNaoki Yoshimura
Jan 7, 2020·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Minoru Miyazato, Asuka Ashikari

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