Dapoxetine, a novel selective serotonin transport inhibitor for the treatment of premature ejaculation

Kendirci, Muammer; Salem, Emad A.; Hellstrom, Wayne J.G.

doi:10.2147/tcrm.2007.3.2.277

Cited by 45 publications

(48 citation statements)

References 90 publications

(145 reference statements)

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“…The pharmacological action of these drugs is thought to inhibit the reuptake of serotonin at the synaptic cleft of the central nervous system (Fuller and Wong 1990). Dapoxetine was developed specifically for the treatment of premature ejaculation (Kendirci et al 2007). Dapoxetine and fluoxetine have similar molecular weights and similar structures with an amine group and a benzene ring as a common structure.…”

Section: Introductionmentioning

confidence: 99%

Effects of dapoxetine on cloned Kv1.5 channels expressed in CHO cells

Jeong

Yoon

Hahn

2012

Naunyn-Schmiedeberg's Arch Pharmacol

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The effects of dapoxetine were examined on cloned Kv1.5 channels stably expressed in Chinese hamster ovary cells using the whole-cell patch clamp technique. Dapoxetine decreased the peak amplitude of Kv1.5 currents and accelerated the decay rate of current inactivation in a concentration-dependent manner with an IC ( 50 ) of 11.6 μM. Kinetic analysis of the time-dependent effects of dapoxetine on Kv1.5 current decay yielded the apparent association (k (+1 )) and dissociation (k (-1 )) rate constants of 2.8 μM(-1) s(-1) and 34.2 s(-1), respectively. The theoretical K ( D ) value, derived by k (-1 )/k (+1 ), yielded 12.3 μM, which was reasonably similar to the IC ( 50 ) value obtained from the concentration-response curve. Dapoxetine decreased the tail current amplitude and slowed the deactivation process of Kv1.5, which resulted in a tail crossover phenomenon. The block by dapoxetine is voltage-dependent and steeply increased at potentials between -10 and +10 mV, which correspond to the voltage range of channel activation. At more depolarized potentials, a weaker voltage dependence was observed (δ=0.31). Dapoxetine had no effect on the steady-state activation of Kv1.5 but shifted the steady-state inactivation curves in a hyperpolarizing direction. Dapoxetine produced a use-dependent block of Kv1.5 at frequencies of 1 and 2 Hz and slowed the time course for recovery of inactivation. These effects were reversible after washout of the drug. Our results indicate that dapoxetine blocks Kv1.5 currents by interacting with the channel in both the open and inactivated states of the channel.

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Section: Introductionmentioning

confidence: 99%

Effects of dapoxetine on cloned Kv1.5 channels expressed in CHO cells

Jeong

Yoon

Hahn

2012

Naunyn-Schmiedeberg's Arch Pharmacol

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“…108,110 One systematic review evaluated the risk-benefit assessment of dapoxetine including withdrawal data from Phase III trials, 111 one review evaluated dapoxetine Phase II trials including pharmacokinetic and safety data 112 and two further effectiveness reviews of SSRIs included studies of dapoxetine and other SSRIs. 65,67 One further RCT was identified that evaluated dapoxetine and dapoxetine plus a PDE5 inhibitor (mirodenafil).…”

Section: Characteristics Of Included Studies: Dapoxetinementioning

confidence: 99%

“…Adverse event and withdrawal data for RCTs from reviews are summarised from the reports by McCarty and Dinsmore, 109 McMahon and Porst, 68 Hutchinson et al 111 and Kendirci et al 112 in Table 20.…”

Section: Assessment Of Safety: Dapoxetine -Adverse Eventsmentioning

confidence: 99%

Interventions to treat premature ejaculation: a systematic review short report

Cooper

James

Kaltenthaler

et al. 2015

Health Technology Assessment

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BackgroundPremature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE can be either lifelong and present since first sexual experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology.J Sex Marital Ther1989;15:130–4). Treatments include behavioural and pharmacological interventions.ObjectiveTo systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE.Data sourcesThe following databases were searched from inception to 6 August 2013 for published and unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects and theHealth Technology Assessmentdatabase; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science. The US Food and Drug Administration website and the European Medicines Agency (EMA) website were also searched.MethodsRandomised controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the absence of RCTs). RCT data were extrapolated from review articles when available. The primary outcome was intravaginal ejaculatory latency time (IELT). Data were meta-analysed when possible. Other outcomes included sexual satisfaction, control over ejaculation, relationship satisfaction, self-esteem, quality of life, treatment acceptability and adverse events (AEs).ResultsA total of 103 studies (102 RCTs, 65 from reviews) were included. RCTs were available for all interventions except yoga. The following interventions demonstrated significant improvements (p < 0.05) in arithmetic mean difference in IELT compared with placebo:topical anaesthetics– eutectic mixture of local anaesthetics (EMLA®, AstraZeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray;selective serotonin reuptake inhibitors(SSRIs) – citalopram (Cipramil®, Lundbeck), escitalopram (Cipralex®, Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy®, Menarini), 30 mg or 60 mg;serotonin–noradrenaline reuptake inhibitors– duloxetine (Cymbalta®, Eli Lilly & Co Ltd);tricyclic antidepressants– inhaled clomipramine 4 mg;phosphodiesterase-5(PDE5)inhibitors– vardenafil (Levitra®, Bayer), tadalafil (Cialis®, Eli Lilly & Co Ltd);opioid analgesics– tramadol (Zydol SR®, Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows:behavioural therapies– improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone;alpha blockers– terazosin (Hytrin®, AMCO) not significantly different to antidepressants in ejaculation control;acupuncture– improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs;Chinese medicine– improvements over treatment as usual;delay device– improvements in IELT when added to stop–start technique;yoga– improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions.LimitationsAlthough data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report.ConclusionsSeveral interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required.Study registrationThis study is registered as PROSPERO CRD42013005289.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…Dapoxetine, on the other hand, is a rapidacting, short-duration SSRI that was developed specifically for on-demand treatment of PE. 5,16 It is administered orally 1 to 3 hours before intercourse. The tricyclic antidepressant clomipramine is also used for PE, but is not very effective.…”

Section: Alvaro Morales CM Md Frcsc Facsmentioning

confidence: 99%

Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment – topical versus systemic

Morales

2012

CUAJ

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Premature ejaculation (PE) is a common sexual dysfunction affecting 20% to 30% of men worldwide. Definitions of PE vary, but it is typically characterized by short intravaginal ejaculatory latency time (IELT) with concomitant sexual dissatisfaction and distress. PE may be lifelong or acquired, but its etiology remains unclear. Treatment of PE typically involves pharmacotherapy, particularly when lifelong. Although there are numerous reports on the offlabel use of selective serotonin reuptake inhibitors (SSRIs) and other compounds, only 2 treatments have been evaluated in randomized controlled phase 3 clinical trials: PSD502 and dapoxetine (SSRI). Both significantly improved IELT and patient-reported outcome domains of ejaculatory control, sexual satisfaction, and distress as measured by the index of premature ejaculation (IPE), compared with placebo. They constitute the focus of this review. Evidence demonstrated that PSD502, dapoxetine and other SSRIs all significantly improve the symptoms of PE. Systemic use of SSRIs presents risks associated with the known pharmacology of this class. PSD502 allows for topical on-demand treatment applied applied immediately before intercourse, and is not associated with systemic adverse events.

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Dapoxetine, a novel selective serotonin transport inhibitor for the treatment of premature ejaculation

Cited by 45 publications

References 90 publications

Effects of dapoxetine on cloned Kv1.5 channels expressed in CHO cells

Effects of dapoxetine on cloned Kv1.5 channels expressed in CHO cells

Interventions to treat premature ejaculation: a systematic review short report

Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment – topical versus systemic

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