OBJECTIVETo assess the efficacy of dapoxetine on demand for premature ejaculation and provide evidence for clinical decision-making.

METHODSWe searched PubMed, Embase, BIOSIS Previews, Cochrane Library, CNKI Database and Wanfang Database for literature on dapoxetine on demand for premature ejaculation. We performed meta-analysis on the identified publications and evaluated its therapeutic efficacy based on the intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGI), and composite PRO criteria for clinical benefit (CCCB).

RESULTSFour relevant studies were included involving 6 081 cases of premature ejaculation. Compared with the placebo controls, the patients treated with dapoxetine on demand showed significant improvement in IELT (WMD = 1.39, 95% CI [1.23, 1.55], P < 0.000 01), PGI (OR = 2.59, 95% CI [2.21, 3.04], P < 0. 000 01), and CCCB (OR = 2.59, 95% CI [1.98, 3.39], P < 0.000 01). There were significant differences between the 60 mg and 30 mg dapoxetine groups in IELT (WMD = 0.46, 95% CI [0.19, 0.74], P = 0.001 0) and PGI (OR = 1.32, 95% CI [1.06, 1.64], P = 0.01), but not in CCCB (OR = 1.39, 95% CI [0.90, 2.15], P = 0.13).

CONCLUSIONDapoxetine on demand can prolong IELT and improve PGI and CCCB, either at the dose of 60 mg or 30 mg, and has an even better efficacy in prolonging IELT and improving PGI at 60 mg.

Benzylamines ; therapeutic use ; Ejaculation ; Humans ; Male ; Naphthalenes ; therapeutic use ; Premature Ejaculation ; drug therapy ; Treatment Outcome

Benzylamines ; Cardiomyopathy, Hypertrophic/drug therapy* ; Humans ; Pharmaceutical Preparations ; Uracil/analogs & derivatives*

The erectile dysfunction (ED) and premature ejaculation (PE) are common medical conditions of male sexual dysfunction that affects the sexual lives of millions of men. While many drugs are now available for treating ED and PE, oral pharmacotherapy represents the first-line option for most patients. Phosphodiesterase type-5 (PDE5) inhibitors are currently the most widely prescribed oral agent and have a very satisfactory efficacy-safety profile in all ED patients' categories. Continuous treatments using PDE5 inhibitors and new agents including fast acting PDE5 inhibitors or other intracellular modulators are now under investigation. ED patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal injection therapy of which efficacy is high but the attrition rate remains significant. Since the pathophysiology of PE is still unclear and there is no approved treatment, it remains to be underdiagnosed and under-treated. The first-line pharmacotherapy for most PE patients is selective serotonin reuptake inhibitors (SSRI) because central 5-hydroxy tryptamine has been implicated as a key mediator of ejaculatory control. Topical anesthetics have also shown varying degrees of efficacy and tolerability. New agents being considered for the on-demand treatment of PE include tramadol and dapoxetine. Therapies for ED or PE will continue to develop as the understanding of those conditions expands. The purpose of this review is to describe the major recent novel advances in the field of medical therapy for the treatment of ED and PE.
Anesthetics ; Benzylamines ; Erectile Dysfunction ; Humans ; Male ; Naphthalenes ; Phosphodiesterase 5 Inhibitors ; Premature Ejaculation ; Serotonin Uptake Inhibitors ; Tramadol ; Tryptamines

Premature ejaculation (PE) is one of the most common sexual dysfunction problems, which has significant adverse effects on the life quality of the patients. Behavioral therapies have been the mainstay of PE management for many years. However, there is inadequate evidence for their long-term benefit. There are currently no medications licensed specifically for the treatment of PE. Current " off-label" pharmacotherapeutic approaches include topical anesthetics, phosphodiesterase-5 inhibitors, and serotonin reuptake inhibitors, all of which, however, fall short of the ideal therapy for PE. In the absence of a cure, the ideal treatment that researches aim at should be tolerable, effective from the first dose, rapid in onset of action, fast in elimination, and available as an oral medication. It is anticipated that agents being developed for the specific indication of PE will come closer to this ideal than the existing pharmacotherapeutic approaches.
Benzylamines ; therapeutic use ; Humans ; Male ; Naphthalenes ; therapeutic use ; Serotonin Uptake Inhibitors ; therapeutic use ; Sexual Dysfunction, Physiological ; drug therapy

Cardiac hypertrophy is an independent risk factor for sudden cardiac death in clinical settings and the incidence of sudden cardiac death and ventricular arrhythmias are closely related. The aim of this study was to determine the effects of the calmodulin-dependent protein kinase (CaMK) II inhibitor, KN-93, on L-type calcium current (I(Ca, L)) and early after-depolarizations (EADs) in hypertrophic cardiomyocytes. A rabbit model of myocardial hypertrophy was constructed through abdominal aortic coarctation (LVH group). The control group (sham group) received a sham operation, in which the abdominal aortic was dissected but not coarcted. Eight weeks later, the degree of left ventricular hypertrophy (LVH) was evaluated using echocardiography. Individual cardiomyocyte was isolated through collagenase digestion. Action potentials (APs) and I(Ca, L) were recorded using the perforated patch clamp technique. APs were recorded under current clamp conditions and I(Ca, L) was recorded under voltage clamp conditions. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were observed under the conditions of low potassium (2 mmol/L), low magnesium (0.25 mmol/L) Tyrode's solution perfusion, and slow frequency (0.25-0.5 Hz) electrical stimulation. The incidence of EADs and I(ca, L) in the hypertrophic cardiomyocytes were also evaluated after treatment with different concentrations of KN-92 (KN-92 group) and KN-93 (KN-93 group). Eight weeks later, the model was successfully established. Under the conditions of low potassium, low magnesium Tyrode's solution perfusion, and slow frequency electrical stimulation, the incidence of EADs was 0/12, 11/12, 10/12, and 5/12 in sham group, LVH group, KN-92 group (0.5 μmol/L), and KN-93 group (0.5 μmol/L), respectively. When the drug concentration was increased to 1 μmol/L in KN-92 group and KN-93 group, the incidence of EADs was 10/12 and 2/12, respectively. At 0 mV, the current density was 6.7±1.0 and 6.3±0.7 PA·PF(-1) in LVH group and sham group, respectively (P>0.05, n=12). When the drug concentration was 0.5 μmol/L in KN-92 and KN-93 groups, the peak I(Ca, L) at 0 mV was decreased by (9.4±2.8)% and (10.5±3.0)% in the hypertrophic cardiomyocytes of the two groups, respectively (P>0.05, n=12). When the drug concentration was increased to 1 μmol/L, the peak I(Ca, L) values were lowered by (13.4±3.7)% and (40±4.9)%, respectively (P<0.01, n=12). KN-93, a specific inhibitor of CaMKII, can effectively inhibit the occurrence of EADs in hypertrophic cardiomyocytes partially by suppressing I(Ca, L), which may be the main action mechanism of KN-93 antagonizing the occurrence of ventricular arrhythmias in hypertrophic myocardium.
Animals ; Benzylamines ; pharmacology ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; antagonists & inhibitors ; metabolism ; Cardiomegaly ; metabolism ; physiopathology ; Female ; Myocytes, Cardiac ; drug effects ; metabolism ; physiology ; Rabbits ; Sulfonamides ; pharmacology

Premature ejaculation (PE) is the most common form of male sexual dysfunction. Until very recently, scientific investigation of PE has been hampered by a lack of standardized definitions and objective, validated questionnaires. In recent years both the definition and the management of PE have changed from the traditional authority-based to a more evidence-based approach. In 2007, the International Society for Sexual Medicine (ISSM) established an ad hoc committee consisting of 21 internationally recognized experts, to establish a new definition of PE including intravaginal ejaculation latency time (IELT). As diagnostic tools, a brief self-administered questionnaire, the premature ejaculation diagnostic tool (PEDT), was developed and validated. Current accepted treatment options of PE include behavior therapy, topical desensitizing agents, selective serotonin reuptake inhibitors (SSRIs), clomipramine, tramadol, PDE-5 inhibitors. However, it should be noted that all of the medications currently used for treatment of PE were originally developed to treat other medical disorders such as depression or erectile dysfunction. Dapoxetine, a new SSRI, has a unique pharmacokinetic profile, with a short time to maximum serum concentration, and rapid elimination. By 24 hours, plasma concentrations are less than 5% of peak values. These attributes make Dapoxetine suitable for on-demand therapy of PE. This paper reviewed new diagnostic tools and treatment options for PE.
Behavior Therapy ; Benzylamines ; Clomipramine ; Depression ; Ejaculation ; Erectile Dysfunction ; Humans ; Male ; Naphthalenes ; Phosphodiesterase 5 Inhibitors ; Plasma ; Premature Ejaculation ; Surveys and Questionnaires ; Serotonin Uptake Inhibitors ; Tramadol

Premature ejaculation (PE) affects the 20~30% men among general population regardless of their age. PE may be classified as lifelong (primary) or acquired (secondary) type. Diagnosis of PE is mainly based on subjective complaints of sexual symptoms. Recently proposed diagnostic system of PE is based on many aspects; intravaginal ejaculatory latency time (IELT), control over ejaculation, stress and interpersonal difficulty according to the PE problem. Standard treatment of lifelong PE is mainly pharmacotherapy. Among many treatment options, selective serotonin reuptake inhibitors (SSRIs) are recommended for off-label use by American Urologic Association and International Consultation on Sexual Medicine. SSRIs were reported to improve the PE symptom by lengthening IELT. However, daily intake of SSRIs often increases the possibility of adverse effects, such as nausea, diarrhea, loss of libido, and even erectile dysfunction. Recently, dapoxetine hydrochloride, newer SSRI with short half life, was tailored to target the PE. Dapoxetine was proved its efficacy on PE over placebo. Clinicians should keep in mind that the sexual dysfunction can be the primary complaints or the results of the intake of antidepressants at the same time.
Antidepressive Agents ; Benzylamines ; Diarrhea ; Ejaculation ; Erectile Dysfunction ; Half-Life ; Humans ; Libido ; Male ; Naphthalenes ; Nausea ; Off-Label Use ; Premature Ejaculation ; Serotonin Uptake Inhibitors

Premature ejaculation (PE) is a most common sexual dysfunction, for which dapoxetine, a novel selective serotonin (5-HT) re-uptake inhibitor (SSRI), is the only licensed oral medicine at present. With the advantages of fast absorption, rapid action, on-demand medication, and short half-life time, dapoxetine has been proved by clinical trials to be effective in prolonging the intravaginal ejaculation latency time (IELT) and improving the overall condition of PE patients in various areas and populations. Compared with the traditional SSRIs, dapoxetine has a better safety and tolerability. The most frequently reported dapoxetine-related adverse events include nausea, diarrhea, headache and dizziness, but with very few severe or serious cases.
Benzylamines ; therapeutic use ; Biomedical Research ; Ejaculation ; drug effects ; Humans ; Male ; Naphthalenes ; therapeutic use ; Premature Ejaculation ; drug therapy ; Reaction Time ; drug effects ; Serotonin Uptake Inhibitors ; therapeutic use ; Treatment Outcome

AIMTo search for some substituted alpha-amino phosphonates as leading compounds with the vasodilator effects.

METHODSTarget compounds were prepared from benzyl aldehyde, piperazine and diethyl phosphite using alcohol as solvent via Mannich-type reaction. In isolated rat aorta and in isolated guinea pig ileum, the vasodilator effects of compounds were investigated and evaluated whether they activated muscarine receptor.

RESULTSSeven compounds of substituted alpha-amino phosphonates have been synthesized and identified by IR, 1H NMR and elemental analysis. Three of them, compound 2a, 2b and 2c have vasodilator activity and do not activate M receptor.

CONCLUSIONTwo (2b and 2c) of them were found to have the notable vasodilator effect, and the rates of relaxing are (67 +/- 21) % and (82 +/- 18)%, separately. But they did not activate M receptors on ileum.

Animals ; Aorta ; drug effects ; Benzylamines ; chemical synthesis ; chemistry ; pharmacology ; Guinea Pigs ; Ileum ; drug effects ; Molecular Structure ; Muscle Contraction ; drug effects ; Organophosphonates ; chemical synthesis ; chemistry ; pharmacology ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; chemistry ; pharmacology

ObjectiveTo evaluate the effect and safety of Yimusake Tablets combined with dapoxetine hydrochloride and either of them used alone in the treatment of premature ejaculation (PE).

METHODSWe randomly assigned 180 PE patients to oral medication of Yimusake Tablets at 1.5 g per night (group A), dapoxetine hydrochloride at 30 mg at 1－3 hours before anticipated sexual activity (group B), the Yimusake Tablets plus dapoxetine hydrochloride simultaneously (group C), all for 8 weeks. After 4 and 8 weeks of medication, we recorded and compared the changes in the intravaginal ejaculation latency time (IELT), measures of the PE profile (PEP), and adverse events among the three groups of patients.

RESULTSThe treatment was accomplished and complete data obtained from 154 of the patients, 56 in group A, 52 in group B, and 46 in group C. After 4 and 8 weeks of medication, the mean IELT was dramatically prolonged in all the three groups as compared with the baseline (P<0.01), most significantly at 8 weeks in group C (［2.08±0.68］ min), followed by B (［1.76±0.52］ min) and A (［1.47±0.44］ min), with statistically significant differences among the three groups (P<0.01). The PEP measures were remarkably improved in group A at 8 weeks (P<0.05), and both in B and C at 4 and 8 weeks (P<0.05), most significantly at 8 weeks in group C (P<0.05), in which the patients scored 1.96±0.77 in perception of control over ejaculation, 2.62±0.98 in satisfaction with sexual intercourse, 3.04±0.62 in PE-related distress, and 3.57±0.80 in PE-induced difficult relationship with their partners, all markedly improved as compared with groups A and B (P<0.05). Adverse reactions were observed in 2 cases (3.6%) in group A, 6 cases (9.6%) in B, and 5 cases (10.9%) in C. No severe adverse events occurred in any of the patients during the study.

CONCLUSIONSCombined medication of Yimusake Tablets and dapoxetine hydrochloride, with its advantages of effectiveness and safety, deserves to be recommended for the treatment of PE.

Administration, Oral ; Adult ; Benzylamines ; therapeutic use ; Coitus ; psychology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Ejaculation ; Humans ; Male ; Naphthalenes ; therapeutic use ; Personal Satisfaction ; Premature Ejaculation ; drug therapy ; Sexual Behavior ; Tablets ; Time Factors ; Treatment Outcome