title: Effect of Duloxetine on Urethral Resting Pressure and on Sphincter Contractility in Response to Coughing and Magnetic Stimulation in Healthy Women.
abstract: OBJECTIVE
  As a proof-of-mechanism (POM) study of drugs developed to treat stress urinary incontinence (SUI) has not been conducted, this urodynamic study in healthy women was performed to determine an appropriate method to confirm POM, and to evaluate the effect of duloxetine, a serotonin and noradrenaline reuptake inhibitor, on urethral resting pressure and on sphincter contractility in response to coughing and magnetic stimulation.
  
  
  METHODS
  The urethral pressure profiles at rest, during coughing and during sacral root magnetic stimulation (SMS), and the motor threshold (MT) for urethral sphincter contraction in response to transcranial magnetic stimulation (TMS) were measured before and 6 h after the administration of 40 mg duloxetine in 10 healthy female subjects.
  
  
  RESULTS
  Oral administration of duloxetine significantly increased the mean and maximal urethral closure pressures at rest over the proximal and middle third of the urethra. During coughing, duloxetine marginally significantly increased the mean distal urethral pressure and significantly reduced the mean delay in the distal urethral pressure peak relative to the vesical peak. Although duloxetine did not change amplitudes of pressure spikes in response to SMS, this drug significantly lowered the MT in response to TMS.
  
  
  CONCLUSIONS
  The proposed method for measuring the urethral resistance in healthy women can be used in POM studies of new drugs developed to treat SUI.
  
  
  BACKGROUND
  UMIN000009096.
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.|Department of Urology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yono
authors.affiliation: Department of Urology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Otani
authors.affiliation: Department of Clinical Pharmacology, Sumida Hospital, Medical Co. LTA, Tokyo, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Furukawa
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Yukikuni
authors.initials: Y
authors.lastname: Sakata
authors.affiliation: Department of Clinical Pharmacology, Nishi-Kumamoto Hospital, Medical Co. LTA, Kumamoto, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Irie
mesh_terms: D000284:Administration, Oral; D000328:Adult; D003371:Cough; D000068736:Duloxetine Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008160:Lumbosacral Plexus; D055909:Magnetic Field Therapy; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D011312:Pressure; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
chemical_list: D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000068736:Duloxetine Hydrochloride
keywords: duloxetine; healthy women; proof-of-mechanism; stress urinary incontinence; urethra