Central nervous system control of the lower urinary tract: new pharmacological approaches to stress urinary incontinence in women.
OBJECTIVE
Despite the prevalence of stress urinary incontinence in women there are no approved drugs for the disease.


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.
Thor
Karl B
KB
Dynogen Pharmaceuticals, Inc., Durham, North Carolina 27708, USA. kthor@dynogenpharma.com
Donatucci
Craig
C
D002490:Central Nervous System / Q000503:physiopathology; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D009130:Muscle, Smooth / Q000503:physiopathology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013876:Thiophenes / Q000627:therapeutic use; D014521:Urethra / Q000294:innervation / Q000503:physiopathology; D001743:Urinary Bladder / Q000503:physiopathology; D014550:Urinary Incontinence, Stress / Q000188:drug therapy* / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects / Q000502:physiology*; D014563:Urodynamics
D000068736:Duloxetine Hydrochloride; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes