Karl B Thor1, Craig Donatucci. 1. Dynogen Pharmaceuticals, Inc., Durham, North Carolina 27708, USA. kthor@dynogenpharma.com
Abstract
PURPOSE: Despite the prevalence of stress urinary incontinence in women there are no approved drugs for the disease. MATERIALS AND METHODS: Designing medical therapies requires a comprehensive understanding of how the internal and external sphincters are neurologically controlled. In this review recent advances in mapping storage and micturition reflexes, and the association of serotonergic and noradrenergic systems with these reflexes are discussed. RESULTS: Urine storage and micturition are controlled by a series of hard wired reflexes that are under the modulatory influence of serotonin and norepinephrine. Augmentation of the serotonergic and noradrenergic systems with duloxetine increases bladder capacity and urethral rhabdosphincter activity. The increase in sphincter activity is mediated by alpha1 adrenergic receptors and 5-hydroxytryptamine receptors. CONCLUSIONS: Increasing rhabdosphincter activity with duloxetine may offer a therapeutic benefit in women with stress urinary incontinence.
PURPOSE: Despite the prevalence of stress urinary incontinence in women there are no approved drugs for the disease. MATERIALS AND METHODS: Designing medical therapies requires a comprehensive understanding of how the internal and external sphincters are neurologically controlled. In this review recent advances in mapping storage and micturition reflexes, and the association of serotonergic and noradrenergic systems with these reflexes are discussed. RESULTS: Urine storage and micturition are controlled by a series of hard wired reflexes that are under the modulatory influence of serotonin and norepinephrine. Augmentation of the serotonergic and noradrenergic systems with duloxetine increases bladder capacity and urethral rhabdosphincter activity. The increase in sphincter activity is mediated by alpha1 adrenergic receptors and 5-hydroxytryptamine receptors. CONCLUSIONS: Increasing rhabdosphincter activity with duloxetine may offer a therapeutic benefit in women with stress urinary incontinence.
Authors: Rachelle Prantil-Baun; William C de Groat; Minoru Miyazato; Michael B Chancellor; Naoki Yoshimura; David A Vorp Journal: Am J Physiol Renal Physiol Date: 2010-05-05
Authors: Madeleine S A Tan; Faraz Honarparvar; James R Falconer; Harendra S Parekh; Preeti Pandey; Dan J Siskind Journal: Psychopharmacology (Berl) Date: 2021-01-07 Impact factor: 4.530