Serotonin and the neurobiology of the ejaculatory threshold

Jong, Trynke R. de; Veening, Jan G.; Waldinger, Marcel D.; Cools, Alexander R.; Olivier, Berend

doi:10.1016/j.neubiorev.2006.01.001

Cited by 84 publications

(57 citation statements)

References 223 publications

(258 reference statements)

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“…1 Several studies have suggested a dysfunction of the serotonin (5-hydroxytryptamine), dopamine, and epinephrine pathways as a biological cause of lifelong PE. [2][3][4][5] Lifelong PE has been reported as the most common sexual disease in young men. 6 Drug treatment of PE with an off-label antidepressant selective serotonin reuptake inhibitor (SSRI) drug, topical anesthetics, and the narcotic analgesic tramadol were the only therapies until dapoxetine introduction.…”

Section: Resultsmentioning

confidence: 99%

Dapoxetine Treatment in Patients With Lifelong Premature Ejaculation: The Reasons of a “Waterloo”

Mondaini

Fusco

Cai

et al. 2013

Urology

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OBJECTIVETo assess both the acceptance and the discontinuation rates from dapoxetine, the first oral pharmacological agent indicated for the treatment of premature ejaculation (PE). METHODSOne hundred twenty consecutive potent patients (mean age 40.3 years; range 18-63 years) seeking medical treatment for lifelong PE were enrolled in a prospective phase II study. Moreover, they were assessed regarding detailed medical and sexual history, intravaginal ejaculatory latency time (IELT), International Index of Erectile Function (IIEF), and complete physical examination. The patients received a dapoxetine prescription (30 mg on demand) and unresponded cases received increased dose (60 mg after 3 months). The patients were evaluated at 1, 3, 6, and 12 months, and requested to complete a multiple-choice global assessment questionnaire regarding specific reasons for eventual therapy discontinuation. RESULTSTwenty-four of the patients (20%) decided not to start dapoxetine. Fear of using a "drug" was the most frequently reported reason for treatment nonacceptance (50%) and the cost of treatment was the reason for 25% of the patients. Ninety-six patients (80%) started the therapy. Twenty-six percent dropped out after 1 month, 42.7% dropped out after 3 months, 18.7% dropped out at 6 months, 2% dropped out at 12 months, and 10.4% are continuing the therapy after 1 year. The main reasons were effect below expectations 24.4%, costs 22.1%, side effects 19.8%, loss of interest in sex 19.8%, and no efficacy 13.9%. CONCLUSIONTwenty percent of lifelong PE patients seeking medical treatment for early ejaculation freely decided not to start treatment with dapoxetine, and roughly 90% of the patients who started therapy discontinued after 1 year. UROLOGY 82: 620e624, 2013. Ó 2013 Elsevier Inc. P remature ejaculation (PE) is a common sexual dysfunction in men characterized by a short time to, and a lack of control over, ejaculation and is associated with distress for patients and their partners.

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Section: Resultsmentioning

confidence: 99%

Dapoxetine Treatment in Patients With Lifelong Premature Ejaculation: The Reasons of a “Waterloo”

Mondaini

Fusco

Cai

et al. 2013

Urology

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“…It is unlikely that SSRI-induced increases in plasma 5-HT contribute to the antidepressant effects of this class of medication. However, it is tempting to speculate that SSRI-induced increases in plasma 5-HT contribute to the ability of SSRIs to increase ejaculatory threshold (de Jong et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Amphetamine Analogs Increase Plasma Serotonin: Implications for Cardiac and Pulmonary Disease

Żółkowska¹,

Rothman²,

Baumann³

2006

J Pharmacol Exp Ther

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Elevations in plasma serotonin (5-HT) have been implicated in the pathogenesis of cardiac and pulmonary disease. Normally, plasma 5-HT concentrations are kept low by transporter-mediated uptake of 5-HT into platelets and by metabolism to 5-hydroxyindoleacetic acid (5-HIAA). Many abused drugs (e.g., substituted amphetamines) and prescribed medications (e.g., fluoxetine) target 5-HT transporters and could thereby influence circulating 5-HT. We evaluated the effects of amphetamines analogs [(Ϯ)-fenfluramine, (Ϯ)-3,4-methylenedioxymethamphetamine, (ϩ)-methamphetamine, (ϩ)-amphetamine, phentermine] on extracellular levels (i.e., plasma levels) of 5-HT and 5-HIAA in blood from catheterized rats. Effects of the 5-HT uptake blocker fluoxetine were examined for comparison. Drugs were tested in vivo and in vitro; plasma indoles were measured using a novel microdialysis method in whole blood. We found that baseline dialysate levels of 5-HT are ϳ0.22 nM, and amphetamine analogs evoke large dose-dependent increases in plasma 5-HT ranging from 4 to 20 nM. The ability of drugs to elevate plasma 5-HT is positively correlated with their potency as 5-HT transporter substrates. Fluoxetine produced small, but significant, increases in plasma 5-HT. Although the drug-evoked 5-HT concentrations are below the micromolar levels required for contraction of pulmonary arteries, they approach concentrations reported to stimulate mitogenesis in pulmonary artery smooth muscle cells. Additional studies are needed to determine the effects of chronic administration of amphetamines on circulating 5-HT.Serotonin (5-hydroxytryptamine, 5-HT) is an endogenous bioactive compound that is widely distributed in neurons, mast cells, enterochromaffin cells, and blood platelets (Cooper et al., 2003;Gershon, 2004). Under normal physiological conditions, plasma 5-HT levels are kept exquisitely low (i.e., Ͻ1 nM) due to transporter-mediated uptake of 5-HT into blood platelets and via metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) by monoamine oxidase (MAO). Included among the many physiological effects of 5-HT are mitogenesis and vasoconstriction. Accordingly, altered regulation of 5-HT levels in blood has been implicated in the pathogenesis of cardiac valvular heart disease (VHD) (Robiolio et al., 1995) and primary pulmonary hypertension (PPH) (MacLean et al., 2000). Many substituted amphetamine analogs (e.g., fenfluramine and aminorex) are substrates for 5-HT transporters (SERTs) and release 5-HT from neurons via reversal of SERT (Rothman et al., 1999). One hypothesis to explain the ability of these agents to increase the risk of developing PPH is that they increase plasma 5-HT by stimulating 5-HT release from platelets (i.e., "the 5-HT hypothesis" of PPH) (MacLean et al., 2000). Others have invoked the same mechanism to explain fenfluramine-induced VHD (Fishman, 1999), although a more likely mechanism in this case involves activation of 5-HT 2B receptors by the N-deethylated metabolite of fenfluramine, norfenfluramine (Rothman et al., 2000...

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“…In addition, studies in humans reported that hyperserotonemia derives in azoospermia (Gonzales et al 1989(Gonzales et al , 1992. Furthermore, in reproductive pathologies such as varicocele, 5-HT blood levels are elevated and it has also been proven that serotoninergic neurotransmission dysfunctions are involved in premature ejaculation (de Jong et al 2006, Chan et al 2008, Motofei 2008. In humans, 5-HT affects the ejaculatory response and sperm transport (Tanrikut & Schlegel 2007, Tanrikut et al 2010.…”

Section: Introductionmentioning

confidence: 99%

Evidence of 5-HT components in human sperm: implications for protein tyrosine phosphorylation and the physiology of motility

Jiménez-Trejo¹,

Tapia-Rodríguez²,

Cerbón³

et al. 2012

Reproduction

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Serotonin (5-hydroxytryptamine; C 10 H 12 N 2 O (5-HT)) is produced in the CNS and in some cells of peripheral tissues. In the mammalian male reproductive system, both 5-HT and tryptophan hydroxylase (TPH) have been described in Leydig cells of the testis and in principal cells of the caput epididymis. In capacitated hamster sperm, it has been shown that 5-HT promotes the acrosomal reaction. The aim of this work was to explore the existence of components of the serotoninergic system and their relevance in human sperm physiology. We used both immunocytochemistry and western blot to detect serotoninergic markers such as 5-HT, TPH1, MAO A , 5-HT 1B , 5-HT 3 , and 5HT T ; HPLC for TPH enzymatic activity; Computer Assisted Semen Analysis assays to measure sperm motility parameters and pharmacological approaches to show the effect of 5-HT in sperm motility and tyrosine phosphorylation was assessed by western blot. We found the presence of serotoninergic markers (5-HT, TPH1, MAO A , 5-HT 1B , 5-HT 2A , 5-HT 3 , 5-HT T , and TPH enzymatic activity) in human sperm. In addition, we observed a significant increase in tyrosine phosphorylation and changes in sperm motility after 5-HT treatment. In conclusion, our data demonstrate the existence of components of a serotoninergic system in human sperm and support the notion for a functional role of 5-HT in mammalian sperm physiology, which can be modulated pharmacologically.

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Serotonin and the neurobiology of the ejaculatory threshold

Cited by 84 publications

References 223 publications

Dapoxetine Treatment in Patients With Lifelong Premature Ejaculation: The Reasons of a “Waterloo”

Dapoxetine Treatment in Patients With Lifelong Premature Ejaculation: The Reasons of a “Waterloo”

Amphetamine Analogs Increase Plasma Serotonin: Implications for Cardiac and Pulmonary Disease

Evidence of 5-HT components in human sperm: implications for protein tyrosine phosphorylation and the physiology of motility

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