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Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. / Klarskov, Niels; Van Till, Oliver; Sawyer, Will; Cernus, Dirk; Sawyer, Will.

I: Neurourology and Urodynamics, Bind 38, Nr. 6, 2019, s. 1700-1706.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Klarskov, N, Van Till, O, Sawyer, W, Cernus, D & Sawyer, W 2019, 'Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women', Neurourology and Urodynamics, bind 38, nr. 6, s. 1700-1706. https://doi.org/10.1002/nau.24045

APA

Klarskov, N., Van Till, O., Sawyer, W., Cernus, D., & Sawyer, W. (2019). Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. Neurourology and Urodynamics, 38(6), 1700-1706. https://doi.org/10.1002/nau.24045

Vancouver

Klarskov N, Van Till O, Sawyer W, Cernus D, Sawyer W. Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. Neurourology and Urodynamics. 2019;38(6):1700-1706. https://doi.org/10.1002/nau.24045

Author

Klarskov, Niels ; Van Till, Oliver ; Sawyer, Will ; Cernus, Dirk ; Sawyer, Will. / Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women. I: Neurourology and Urodynamics. 2019 ; Bind 38, Nr. 6. s. 1700-1706.

Bibtex

@article{6a5fd2b2c9964d8f9b360ea44e250247,
title = "Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women",
abstract = "AIMS: To evaluate the effect of ASP2205, a selective serotonin 5-HT2c receptor agonist, and Duloxetine on the urethral pressure in healthy female subjects.METHODS: Healthy females aged 18 to 55 years were recruited for this phase 1, single site, placebo-controlled, randomized, four-period, cross-over study. The interventions were single oral doses of 10 and 60 mg ASP2205, 80 mg duloxetine, and placebo. As a pharmacodynamics endpoint, opening urethral pressure (OUP), corrected for placebo, was measured using urethral pressure reflectometry under both resting and squeezing condition of the pelvic floor at predose and 3, 6, 12, and 24 hours after dosing. Safety and tolerability of ASP2205 were also compared with duloxetine and placebo.RESULTS: Eighteen healthy women signed informed consent, however, one dropped out before dosing and one dropped out after the first period, therefore, 16 subjects completed the study. Duloxetine significantly increased the OUP during both resting and squeezing condition (maximal increase 18.1 and 16.8 cmH2 O, respectively). Both doses of ASP2205 did not increase OUP at any time point. During squeezing OUP decreased significantly in the ASP2205 60 mg group from 6 to 24 hours after dosing. All subjects experienced predominantly central nervous system-related side effects (eg, dizziness and nausea) during ASP2205 treatment, which was most pronounced at 60 mg.CONCLUSIONS: ASP2205, a serotonin 5-HT2c receptor agonist, does not increase the urethral pressure and it is therefore unlikely that 5-HT 2c receptor agonists can be used as a treatment for stress urinary incontinence. ASP2205 was less well tolerated than the high dose of duloxetine.",
keywords = "Adolescent, Adult, Azepines/pharmacology, Cross-Over Studies, Duloxetine Hydrochloride/pharmacology, Female, Healthy Volunteers, Humans, Middle Aged, Pressure, Quinolines/pharmacology, Serotonin 5-HT2 Receptor Agonists/pharmacology, Treatment Outcome, Urethra/drug effects, Urinary Incontinence, Stress/drug therapy, Young Adult",
author = "Niels Klarskov and {Van Till}, Oliver and Will Sawyer and Dirk Cernus and Will Sawyer",
year = "2019",
doi = "10.1002/nau.24045",
language = "English",
volume = "38",
pages = "1700--1706",
journal = "Neurourology and Urodynamics",
issn = "0733-2467",
publisher = "JohnWiley & Sons, Inc.",
number = "6",

}

RIS

TY - JOUR

T1 - Effect of a 5-HT2c receptor agonist on urethral closure mechanism in healthy women

AU - Klarskov, Niels

AU - Van Till, Oliver

AU - Sawyer, Will

AU - Cernus, Dirk

AU - Sawyer, Will

PY - 2019

Y1 - 2019

N2 - AIMS: To evaluate the effect of ASP2205, a selective serotonin 5-HT2c receptor agonist, and Duloxetine on the urethral pressure in healthy female subjects.METHODS: Healthy females aged 18 to 55 years were recruited for this phase 1, single site, placebo-controlled, randomized, four-period, cross-over study. The interventions were single oral doses of 10 and 60 mg ASP2205, 80 mg duloxetine, and placebo. As a pharmacodynamics endpoint, opening urethral pressure (OUP), corrected for placebo, was measured using urethral pressure reflectometry under both resting and squeezing condition of the pelvic floor at predose and 3, 6, 12, and 24 hours after dosing. Safety and tolerability of ASP2205 were also compared with duloxetine and placebo.RESULTS: Eighteen healthy women signed informed consent, however, one dropped out before dosing and one dropped out after the first period, therefore, 16 subjects completed the study. Duloxetine significantly increased the OUP during both resting and squeezing condition (maximal increase 18.1 and 16.8 cmH2 O, respectively). Both doses of ASP2205 did not increase OUP at any time point. During squeezing OUP decreased significantly in the ASP2205 60 mg group from 6 to 24 hours after dosing. All subjects experienced predominantly central nervous system-related side effects (eg, dizziness and nausea) during ASP2205 treatment, which was most pronounced at 60 mg.CONCLUSIONS: ASP2205, a serotonin 5-HT2c receptor agonist, does not increase the urethral pressure and it is therefore unlikely that 5-HT 2c receptor agonists can be used as a treatment for stress urinary incontinence. ASP2205 was less well tolerated than the high dose of duloxetine.

AB - AIMS: To evaluate the effect of ASP2205, a selective serotonin 5-HT2c receptor agonist, and Duloxetine on the urethral pressure in healthy female subjects.METHODS: Healthy females aged 18 to 55 years were recruited for this phase 1, single site, placebo-controlled, randomized, four-period, cross-over study. The interventions were single oral doses of 10 and 60 mg ASP2205, 80 mg duloxetine, and placebo. As a pharmacodynamics endpoint, opening urethral pressure (OUP), corrected for placebo, was measured using urethral pressure reflectometry under both resting and squeezing condition of the pelvic floor at predose and 3, 6, 12, and 24 hours after dosing. Safety and tolerability of ASP2205 were also compared with duloxetine and placebo.RESULTS: Eighteen healthy women signed informed consent, however, one dropped out before dosing and one dropped out after the first period, therefore, 16 subjects completed the study. Duloxetine significantly increased the OUP during both resting and squeezing condition (maximal increase 18.1 and 16.8 cmH2 O, respectively). Both doses of ASP2205 did not increase OUP at any time point. During squeezing OUP decreased significantly in the ASP2205 60 mg group from 6 to 24 hours after dosing. All subjects experienced predominantly central nervous system-related side effects (eg, dizziness and nausea) during ASP2205 treatment, which was most pronounced at 60 mg.CONCLUSIONS: ASP2205, a serotonin 5-HT2c receptor agonist, does not increase the urethral pressure and it is therefore unlikely that 5-HT 2c receptor agonists can be used as a treatment for stress urinary incontinence. ASP2205 was less well tolerated than the high dose of duloxetine.

KW - Adolescent

KW - Adult

KW - Azepines/pharmacology

KW - Cross-Over Studies

KW - Duloxetine Hydrochloride/pharmacology

KW - Female

KW - Healthy Volunteers

KW - Humans

KW - Middle Aged

KW - Pressure

KW - Quinolines/pharmacology

KW - Serotonin 5-HT2 Receptor Agonists/pharmacology

KW - Treatment Outcome

KW - Urethra/drug effects

KW - Urinary Incontinence, Stress/drug therapy

KW - Young Adult

U2 - 10.1002/nau.24045

DO - 10.1002/nau.24045

M3 - Journal article

C2 - 31129930

VL - 38

SP - 1700

EP - 1706

JO - Neurourology and Urodynamics

JF - Neurourology and Urodynamics

SN - 0733-2467

IS - 6

ER -

ID: 241579510