Comparison of paroxetine and dapoxetine, a novel selective serotonin reuptake inhibitor in the treatment of premature ejaculation

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation （PE）, Our objective in this study was to characterize the efficacy of on-demand dapoxetine （30 and 60 mg） and daily paroxetine （20 mg） usage in treating PE, We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50, Group 1 were treated with on-demand dapoxetine （30 mg）, Group 2 with on-demand dapoxetine （60 mg） and Group 3 with daily paroxetine （20 rag）, Our outcome measurement was increased from baseline intravaginal ejaculatory latency time （IELT） after treatment, The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group （P 〈 0,01）, 30 mg dapoxetine group （P 〈 0,01） and 60 mg dapoxetine group （P 〈 0.01）, respectively, The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups （P 〉 0,05）, while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine （P〈 0.05） and paroxetine （P〈 0.01） groups, Dapoxetine （60 mg） 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.

Assessment the effect of Dapoxetine and/or Acetaminophen in rats;neurochemicals and oxidative stress biomarkers evaluation

Dapoxetine is a newer anti-depressant that is used for severe forms of depression via selective serotonin reuptake inhibition conduit.We aimed to evaluate the effect of different doses of dapoxetine lonely or with acetaminophen(AMP).Seven groups of albino rats were used where dapoxetine was administered orally at the doses of 3,5,and 8 mg/kg body weight for a period of 14 days in groups 2,4,and 6,respectively.AMP(67.5 mg/kg body weight)was co-administered with dapoxetine(3,5,and 8 mg/kg body weight)for 14 days in groups 3,5 and 7,respectively.Dapoxetine in mid and high dose plus AMP increased body weight and hematological parameters.Ambulation and rearing were declined with mid and high doses of dapoxetine+AMP,contrary to grooming.Struggling was decreased with high doses of dapoxetine+AMP.High dose of dapoxetine+AMP induced lowering of serotonin and dopamine as well as increasing of cholinesterase.Brain derived neurotrophic factor was decreased in all groups.Oxidative stress biomarkers were augmented with high dose of dapoxetine+AMP.High doses of dapoxetine and/or AMP induced loss of the Purkinje cell layer at cerebellum.The high dose of dapoxetine+AMP denotes behavioral,histopathological and neurochemical alterations,even though no serotonin syndrome occurs.

The effect of 8-OH-DPAT and dapoxetine on gene expression in the brain of male rats during ejaculation

The 5-HT_(1A) receptor agonist 8-hydroxy-2-[di-n-propylamino] tetralin(8-OH-DPAT) promotes ejaculation of male rats, whereas dapoxetine delays this process. However, the gene expression profile of the brain at ejaculation following administrationof these two compounds has not been fully elucidated. In the present study, a transcriptomic Body Map was generated by conducting mRNA-Seq on brain samples of male Sprague–Dawley rats. The study included four groups: pre-copulatory control(CK) group,ejaculation(EJ) group, 0.5 mg/kg 8-OH-DPAT-ejaculation group(DPAT), and 60 mg/kg dapoxetineejaculation(DAP) group. The resulting analysis generated an average of approximately 47 million sequence reads. Significant differences in the gene expression profiles of the aforementioned groups were observed in the EJ(257 genes), DPAT(349 genes) and the DAP(207 genes) compared with the control rats. The results indicate that the expression of Drd1 and Slc6a3 was significantly different after treatment with 8-OH-DPAT, whereas the expression of Drd4 was significantly different after treatment with dapoxetine. Other genes, such as Wnt9b, Cdkn1 a and Fosb, exhibited significant differences in expression after the two treatments and are related to bladder cancer, renal cell carcinoma and sexual addiction. The present study reveals the basic pattern of gene expression that was activated at ejaculation in the presence of 8-OH-DPAT or dapoxetine, providing preliminary gene expression information during rat ejaculation.

Current therapeutic strategies for premature ejaculation and future perspectives

Premature ejaculation （PE） is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ＇off-label＇, some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE.

新型液相色谱-荧光检测法测定药物剂型和人血浆中的他达拉非和盐酸达泊西汀(英文)

Tadalafil(TAD)and dapoxetine HCl(DAP)are recently co-formulated and both show native fluorescence.Therefore,a novel,accurate,specific and sensitive reversed-phase high performance liquid chromatographic method with fluorescence detection was developed and validated for their separation and quantitation in dosage form and human plasma using avanafil as an internal standard(IS).Separation was achieved using isocratic elution within 7.0 min on C18column and acetonitrile-0.15%triethylamine(40∶60,v/v;pH 4)as a mobile phase.The flow rate was 1.0 mL/min and the detection was time-programmed at 330,410 and 370 nm for TAD,DAP and IS,respectively,after excitation at 236 nm.The linear ranges from 0.01 to 30.00μg/mL for each drug with the limits of detection of 4.20 and 7.20 ng/mL for TAD and DAP,respectively.The method was validated in accordance to the International Conference on Harmonization(ICH)guidelines and was successfully applied to spiked human plasma with mean recoveries of 98.17%and 98.83%for TAD and DAP respectively.

Efficacy and Safety of Qiaoshao Formula(翘芍方) on Patients with Lifelong Premature Ejaculation of Gan(Liver) Depression and Shen(Kidney) Deficiency Syndrome:A Randomized Controlled Trial

Objective： To observe the efficacy and safety of Qiaoshao Formula（翘芍方, QSF） on patients with lifelong premature ejaculation（LPE） of Gan（Liver） depression and Shen（Kidney） deficiency syndrome. Methods： A total of 60 LPE patients were randomly divided into treatment（QSF） and control（dapoxetine） groups. The treatment group received QSF twice a day and the control group received dapoxetine 1 to 2 h prior to planned sexual intercourse for 4 weeks. The outcomes included intra-vaginal ejaculation latency time（IELT）, premature ejaculation diagnostic tool（PEDT）, clinical global impression of change（CGIC）, scores of Chinese medicine symptoms（CMSS）, sex life satisfaction（SLS） and adverse events（AEs）. Results： In the treatment group, the median IELT was 3 min vs. 1.5 min before and after treatment（P〈0.05）. PEDT in the treatment group was reduced to 11.76±1.68 from 15.83±2.30 after treatment（P〈0.05）. Besides, patient＇s SLS was improved from 1.30±0.05 to 6.30±0.04（P〈0.05）, and spouse＇s SLS was increased from 1.30±0.08 to 6.10±0.06（P〈0.05）; CMSS was decrease from 14.86±3.02 to 9.62±2.87（P〈0.05）. In addition, no significant AE was observed in both groups. Conclusion： QSF may be effective and safe on LPE patients with Gan depression and Shen deficiency syndrome.