Increasing Effects of Selective 5-Hydroxytryptamine Type 2C Receptor Stimulation on Evoked Momentary Urethral Closure in Female Rats and Humans

Izumi, Kiyotaka; Nagata, Hiroshi; O'Connell, Gale; Kato, Takuya; Imanishi, Akihito; Kuno, Miyuki; Okanishi, Satoshi; Yoshikawa, K; Nishiyama, Yuya

doi:10.1124/jpet.121.000573

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…Contrary to expectations, the 5‐HT 2C receptor agonist exerted a dose‐dependent decrease in urethral pressure compared to placebo 13 . Yet, a recent study demonstrated that another selective 5‐HT 2C agonist (TAK‐233) lowered the threshold for urethral sphincter contraction induced by transcranial magnetic stimulation in healthy women, indicating that 5‐HT 2C receptors might enhance the active urethral‐closing reflex rather than the resting urethral pressure 14 …”

Section: Introductionmentioning

confidence: 72%

“…13 Yet, a recent study demonstrated that another selective 5-HT 2C agonist (TAK-233) lowered the threshold for urethral sphincter contraction induced by transcranial magnetic stimulation in healthy women, indicating that 5-HT 2C receptors might enhance the active urethral-closing reflex rather than the resting urethral pressure. 14 Meanwhile, several epidemiological studies have demonstrated a positive association between exposure to serotonergic antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and urinary incontinence. 15,16 Taken together, these findings question the notion that stimulation of centrally-activated 5-HT receptors generally enhances continence.…”

Section: Introductionmentioning

confidence: 99%

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Effect of single doses of citalopram and reboxetine on urethral pressure: A randomized, double‐blind, placebo‐ and active‐controlled three‐period crossover study in healthy women

Christoffersen

Kornholt

Riis

et al. 2022

Neurourology and Urodynamics

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Aims: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI. However, the literature findings are conflicting. This study aimed to evaluate citalopram's effect on opening urethral pressure (OUP) in healthy women. Methods: We conducted a randomized, double-blind, placebo-and activecontrolled crossover study in 24 healthy women. On three study days, which were separated by 8 days of washout, the subjects received single doses of either 40 mg citalopram (and placebo reboxetine ), 8 mg reboxetine (and placebo citalopram ), or two placebos. Study drugs were administered at a 1-h interval due to a difference in estimated time to peak plasma concentration (t max ). We measured OUP with urethral pressure reflectometry under both resting and squeezing conditions of the pelvic floor at estimated t max for both study drugs (one timepoint).Results: Compared to placebo, citalopram increased OUP by 6.6 cmH 2 0 (95% confidence interval [CI] 0.04-13.1, p = 0.048) in resting condition. In squeezing condition, OUP increased by 7.1 cmH 2 0 (95% CI: 1.3-12.9, p = 0.01). Reboxetine increased OUP by 30.0 cmH 2 0 in resting condition compared to placebo (95% CI: 23.5-36.5, p < 0.001), and 27.0 cmH 2 0 (95% CI: 21.2-32.8, p < 0.001) in squeezing condition. Conclusion: Citalopram increased OUP slightly compared to placebo suggesting that SSRI treatment does not induce or aggravate SUI.

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Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Effect of single doses of citalopram and reboxetine on urethral pressure: A randomized, double‐blind, placebo‐ and active‐controlled three‐period crossover study in healthy women

Christoffersen

Kornholt

Riis

et al. 2022

Neurourology and Urodynamics

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“…The phase I trial (Clinical trials ID: NCT02113020) was undertaken in 2014; however, there are no published results in this regard. It was announced in 2016 that Takeda and Frazier had partnered to develop this breakthrough drug [ 37 , 38 ].…”

Section: Literature Descriptionmentioning

confidence: 99%

Pharmacotherapy in Stress Urinary Incontinence; A Literature Review

Tabei,

Baas,

Mahdy

2024

Curr Urol Rep

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Purpose of Review Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress made in surgical techniques, pharmacotherapy has not yielded substantial outcomes within the clinical domain. This review aims to present a comprehensive overview of the existing pharmacotherapy options for stress urinary incontinence (SUI) and the emerging therapeutic targets in this field. Recent Findings One meta-analysis demonstrated that α-adrenergic medications are more efficacious in improving rather than curing SUI symptoms. One trial showed reduced pad weight gain with PSD-503, a locally administered α-adrenergic receptor agonist. New data show that duloxetine’s risk outweighs its benefits. One small-scale trial was found to support the use of locally administered estriol in improving subjective outcomes. Emerging targets include serotonin 5HT2C agonists, selective inhibitors of norepinephrine uptake, and myostatin inhibitors. Summary Only one of the evaluated drugs, duloxetine, has been approved by some countries. Currently, trials are evaluating novel targets. Systemic adverse effects such as gastrointestinal upset with duloxetine and orthostatic hypotension with α-adrenoceptor agonists have hampered the efficacy of drugs used to treat SUI in women and men.

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Spinal Cord

Yoshiyama

Κakizaki

2023

Handbook of Neurourology

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Increasing Effects of Selective 5-Hydroxytryptamine Type 2C Receptor Stimulation on Evoked Momentary Urethral Closure in Female Rats and Humans

Cited by 5 publications

References 23 publications

Effect of single doses of citalopram and reboxetine on urethral pressure: A randomized, double‐blind, placebo‐ and active‐controlled three‐period crossover study in healthy women

Effect of single doses of citalopram and reboxetine on urethral pressure: A randomized, double‐blind, placebo‐ and active‐controlled three‐period crossover study in healthy women

Pharmacotherapy in Stress Urinary Incontinence; A Literature Review

Spinal Cord

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