Association between 5-HTTLPR and STin2 VNTR polymorphisms in the serotonin transporter gene and clinical response of a selective serotonin reuptake inhibitor (dapoxetine) in lifelong premature ejaculation
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SUBMITTER: Abdullah
PROVIDER: S-EPMC9532033 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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| S-EPMC5753546 | biostudies-literature
Project description: Not available
| S-EPMC5676435 | biostudies-literature
Project description:BackgroundPremature ejaculation (PE) is the most common male sexual complaint. Off-label oral selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of PE. Dapoxetine is a short-acting SSRI specifically designed for on-demand use. The objective of this communication is to summarize the clinical and physiological evidence regarding the role of the serotonergic pathway and specifically dapoxetine in the treatment of PE.MethodsA PubMed search was conducted on articles reporting data on dapoxetine for the treatment of PE. Articles describing the pathophysiology and treatment options for PE were additionally included for review.ResultsThe etiology of PE is multi-factorial in nature. There are many treatment options for PE such as psychological/behavioral therapy, topical anesthetic agents, phosphodiesterase type 5 (PDE-5) inhibitors, and tramadol hydrochloride. SSRIs play a major role in PE treatment. Animal and clinical studies in addition to its pharmacokinetic document dapoxetine's clinical efficacy and safety for on-demand treatment of PE.ConclusionsDapoxetine demonstrates clinical efficacy and a favorable side effect profile. Dapoxetine is currently the oral drug of choice for on-demand treatment of PE.
| S-EPMC4708110 | biostudies-literature
Project description:BACKGROUND This study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications. MATERIAL AND METHODS A total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L'L' genotype (OR=0.37; 95%CI=0.15-0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes. CONCLUSIONS Contrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies.
| S-EPMC4920104 | biostudies-literature
Project description:We evaluated the genotypes of the serotonin transporter gene (5-HTT) in patients with premature ejaculation (PE) to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene (5-HTTLPR) were determined. The 5-HTTLPR (serotonin transporter promoter gene) genotypes in PE patients vs. controls were distributed as follows: L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene: LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the chi2-test. The short (S) allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls (P<0.05). We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup (such as primary and secondary PE) responses to selective serotonin reuptake inhibitors as well as ethnic differences.
| S-EPMC3735292 | biostudies-other
Project description:Given that sexual behavior is usually pleasurable and highly rewarding, it is surprising that there is as yet no known research to empirically assess how premature ejaculation (PE) patients respond to the rewarding aspect of sexual behavior. This study was designed to address this issue by evaluating how these men respond to the anticipation and hedonic experience of sexual rewards in comparison to non-sexual rewards. Thirty lifelong PE patients and thirty healthy controls (HCs) performed the incentive delay task manipulating both erotic and monetary rewards. Compared to HCs, lifelong PE patients exhibited significantly faster RTs to erotic cues than to monetary cues during reward anticipation. Meanwhile, hedonic experience ratings after obtaining the actual reward showed that erotic rewards were rated as more pleasant than monetary rewards only by lifelong PE patients, which was driven by a decreased sensitivity to experienced monetary rewards in lifelong PE patients compared to HCs. These findings indicate the existence of dysfunctional reward processing in lifelong PE patients, which is characterized by increased incentive motivation elicited by sexual cues and reduced hedonic impact of nonsexual rewards. This study may offer an insightful clue regarding how PE is related to the abnormal regulation of the rewarding aspect of sexual behavior.
| S-EPMC10579392 | biostudies-literature
Project description:BackgroundLifelong premature ejaculation (LPE) is one of the most common ejaculatory dysfunctions in men. The serotonin (5-HT) synthesis rate-limiting enzyme (TPH2) and receptor (HTR1A) in the 5-HT regulatory system may play a key role in the pathogenesis of LPE. However, there are few studies on the effects of TPH2 and HTR1A polymorphisms on LPE risk. We speculated that TPH2 and HTR1A polymorphisms may affect the occurrence and development of LPE in the Chinese Han population.MethodsIn this study, 91 patients with LPE and 362 normal controls aged 18 to 64 years were enrolled in the male urology department of Hainan General Hospital in China from January 2016 to December 2018. The SNPs in HTR1A and TPH2, which are related to 5-HT regulation, were selected as indexes to genotype the collected blood samples of participants. Logistic regression was used to analyze the correlation between SNPs of HTR1A and TPH2 with LPE susceptibility, as well as the relationship with leptin, 5-HT and folic acid levels.ResultsThe results revealed that HTR1A-rs6295 increased LPE risk in recessive model. Rs11178996 in TPH2 significantly reduced susceptibility to LPE in allelic (odds ratio (OR) = 0.68, 95% confidence interval (95% CI) = 0.49-0.96, p = 0.027), codominant (OR = 0.58, 95% CI = 0.35-0.98, p = 0.040), dominant (OR = 0.58, 95% CI = 0.36-0.92, p = 0.020), and additive (OR = 0.71, 95% CI = 0.52-0.98, p = 0.039) models. Grs11179041Trs10879352 could reduce the risk of LPE (OR = 0.44, 95% CI = 0.22-0.90, p = 0.024) by haplotype analysis.ConclusionHTR1A-rs6295 and TPH2-rs11178996 are associated with LPE risk in the Chinese Han population based on the finding of this study.
| S-EPMC10170821 | biostudies-literature
Project description:Premature ejaculation (PE) is the most common male sexual dysfunction. The brain disturbances that cause this disorder remain poorly understood. This study aimed to investigate how the morphology of cortical and subcortical brain structures differed in PE, how these morphologic differences were associated with severity measures of PE, such as intravaginal ejaculatory latency time (IELT), and how these cortical and subcortical structures were causally connected through mediation analysis. Anatomical MRI scans were acquired from 39 male participants, 23 with PE (28.78 ± 4.32 years), and 16 without PE (27.88 ± 3.65 years). We used a subcortical analysis package within FSL to perform subcortical shape segmentation and statistical analysis. The PE group was compared with the normal control (NC) group in the shapes of 15 subcortical structures with general linear models [p < 0.05, family-wise error (FWE)-corrected]. We analyzed the cortical complexity revealed by the gyrification index using the Computational Anatomy Toolbox (CAT12). Vertex-wise shape analyses revealed outward shape deformations (expansions) in the left hippocampus and bilateral thalamus. Gyrification index analyses revealed that the right orbital frontal cortex and the right nucleus accumbens had greater complexity in PE patients. The shape deformations were positively correlated with the IELTs in the NC group, while this relationship was interrupted in the PE group. PE is associated with outward deformations of the subcortical surfaces and more complexity of the cortical structures. These morphological differences may be the basis of the brain functional alterations underlying PE.
| S-EPMC7387657 | biostudies-literature
Project description:Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally approved antiviral drugs for the treatment of ZIKV infection, and symptomatic management remains the primary clinical approach. Consequently, the exploration of safe and effective anti-ZIKV drugs has emerged as a paramount imperative in ZIKV control efforts. In this study, we performed a screening of a compound library consisting of 1789 FDA-approved drugs to identify potential agents with anti-ZIKV activity. We have identified dapoxetine, an orally administered selective serotonin reuptake inhibitor (SSRI) commonly employed for the clinical management of premature ejaculation (PE), as a potential inhibitor of ZIKV RNA-dependent RNA polymerase (RdRp). Consequently, we conducted surface plasmon resonance (SPR) analysis to validate the specific binding of dapoxetine to ZIKV RdRp, and further evaluated its inhibitory effect on ZIKV RdRp synthesis using the ZIKV Gluc reporter gene assay. Furthermore, we substantiated the efficacy of dapoxetine in suppressing intracellular replication of ZIKV, thereby demonstrating a concentration-dependent antiviral effect (EC50 values ranging from 4.20 μM to 12.6 μM) and negligible cytotoxicity (CC50 > 50 μM) across diverse cell lines. Moreover, cell fluorescence staining and Western blotting assays revealed that dapoxetine effectively reduced the expression of ZIKV proteins. Collectively, our findings suggest that dapoxetine exhibits anti-ZIKV effects by inhibiting ZIKV RdRp activity, positioning it as a potential candidate for clinical therapeutic intervention against ZIKV infection.
| S-EPMC10745718 | biostudies-literature
Project description:Cesium-gold (Cs-Au) nanoparticles are shown to be analytically advantageous for the electroanalytical sensing of dapoxetine (DPX), a serotonin reuptake inhibitor used for the treatment of premature ejaculation. The Cs-Au nanoparticles are electrically wired and supported upon mass producible, economical screen-printed electrochemical sensing platforms and are characterized electrochemically (cyclic voltammetry and electrochemical impedance spectroscopy) and physiochemically (field emission scanning electron microscopy and energy dispersive X-ray analysis). The face-centered design was applied to optimize the significant experimental factors by using square wave voltammetry. The Cs-Au-based sensor is found to exhibit a large linear range (10-7 to 10-4 M) with a good analytical linearity with the limits of detection and quantification corresponding to 2.50 × 10-10 and 8.33 × 10-8 M, respectively. The developed sensor was successfully applied in the quantification of DPX in the presence of sildenafil, both of which are commonly found within combined dose tablet pharmaceutical formulations. The proposed DPX electrochemical Cs-Au-based sensor has the advantages of being single-shot and disposable and is shown to be successful in determining DPX in pharmaceutical formulations, human urine, and serum samples with acceptable recoveries.
| S-EPMC6044806 | biostudies-literature