An update on the treatment of premature ejaculation: A systematic review

Saleh, Ramadan; Majzoub, Ahmad; El‐Hamd, Mohammed Abu

doi:10.1080/2090598x.2021.1943273

Cited by 15 publications

(16 citation statements)

References 156 publications

(245 reference statements)

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“…9 The clinical use of tricyclic antidepressants has been associated with delayed ejaculation, 10 and the tricyclic antidepressant clomipramine has therapeutic indication in the control of premature ejaculation in man. [11][12][13] Lower urinary tract symptoms (LUTSs) are generally treated with α 1 -adrenergic receptor blockers, but reduced ejaculate volume, absence of ejaculate, and retrograde ejaculation are observed in 4%-11% of patients. [14][15] Since both tricyclic antidepressants and α 1 -adrenergic receptor antagonists are potent and selective 6-ND receptor antagonists in the rat vas deferens, these findings open the exciting possibility that these drugs could have similar mechanism in the human vas deferens.…”

Section: Introductionmentioning

confidence: 99%

“…The clinical use of tricyclic antidepressants has been associated with delayed ejaculation, 10 and the tricyclic antidepressant clomipramine has therapeutic indication in the control of premature ejaculation in man 11–13 . Lower urinary tract symptoms (LUTSs) are generally treated with α 1 ‐adrenergic receptor blockers, but reduced ejaculate volume, absence of ejaculate, and retrograde ejaculation are observed in 4%–11% of patients 14–15 …”

Section: Introductionmentioning

confidence: 99%

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6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

et al. 2022

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Background Rat isolated vas deferens releases 6‐nitrodopamine (6‐ND), and the spasmogenic activity of this novel catecholamine is significantly reduced by tricyclic compounds such as amitriptyline, desipramine, and carbamazepine and by antagonists of the α1‐adrenergic receptors such as doxazosin, tamsulosin, and prazosin. Objectives To investigate the liberation of 6‐ND by human epididymal vas deferens (HEVDs) and its pharmacological actions. Methods The in vitro liberation of 6‐ND, dopamine, noradrenaline, and adrenaline from human vas deferens was evaluated by LC‐MS/MS. The contractile effect of the catecholamines in HEVDs was investigated in vitro. The action of tricyclic antidepressants was evaluated on the spasmogenic activity ellicited by the catecholamines and by the electric‐field stimulation (EFS). The tissue was also incubated with the inhibitor of nitric oxide (NO) synthase L‐NAME and the release of catecholamines and the contractile response to EFS were assessed. Results 6‐ND is the major catecholamine released from human vas deferens and its synthesis/release is inhibited by NO inhibition. The spasmogenic activity elicited by EFS in the human vas deferens was blocked by tricyclic antidepressants only at concentrations that selectively antagonize 6‐ND induced contractions of the human vas deferens, without affecting the spasmogenic activity induced by dopamine, noradrenaline, and adrenaline in this tissue. Incubation of the vas deferens with L‐NAME reduced both the 6‐ND release and the contractions induced by EFS. Discussion and conclusion 6‐ND should be considered a major endogenous modulator of human vas deferens contractility and possibly plays a pivotal role in the emission process of ejaculation. It offers a novel and shared mechanism of action for tricyclic antidepressants and α1‐adrenergic receptor antagonists.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

et al. 2022

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“…44 According to previous studies, the antidepressant SSRIs increase the 5-HT level by blocking the 5-HT transporter (5-HTT) and thereby decreasing the reuptake of 5-HT in the presynaptic nerve terminal. 49 At present, SSRI has become the first choice for the treatment of PE, and dapoxetine hydrochloride is the first drug specially used for the treatment of PE in the world. Its efficacy and safety in the treatment of PE have been confirmed by many large international multicenter randomized controlled studies.…”

Section: Discussionmentioning

confidence: 99%

Selective serotonin reuptake inhibitors combined with traditional Chinese medicine for premature ejaculation: A systematic review and meta‐analysis

Chang

Chen

et al. 2022

Andrology

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Background Premature ejaculation (PE) is still a tough problem in drug treatment. Many clinical trials have proven that traditional Chinese medicine (TCM) has a significant effect in the treatment of PE. This article aims to provide the latest evidence for the efficacy and safety of TCM combined with selective serotonin reuptake inhibitors (SSRIs) in the treatment of PE. Methods We looked for randomized controlled trials (RCTs) from China National Knowledge Infrastructure, Wanfang, VIP Database, MEDLINE, PubMed, Web of Science, EMBASE, and Cochrane Library until June 30, 2022. STATA 15.1 software was used to analyze all data for this article. The quality of the included articles was evaluated using the Cochrane Reviewer's Handbook 5.3. Results Finally, we selected 16 high‐quality RCTs in our meta‐analysis, which containing 889 patients. Meta‐analysis suggested that, compared with SSRIs alone, combination of TCM with SSRIs increased significantly intravaginal ejaculation latencv time and the scores of ejaculation control ability, sexual life satisfaction, PE‐related distress, and communication difficulties between partners related to PE. Also, there was no significant difference in adverse effects between the two groups. In addition, the results of publication bias test showed that no significant bias occurred. Conclusion The combined use of TCM and SSRIs has significant effect in the treatment of PE compared with SSRIs monotherapy and was generally well tolerated. Due to the small sample size, multicenter and large sample RCT is still needed in the future to further confirm the effectiveness and safety of TCM combined with SSRIs in the treatment of PE.

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“…Dapoxetine and local anesthetics have been approved in several countries within Europe. On the other hand, no pharmacological treatments have been approved for PE by the Food and Drug Administration in the United States [5,6]. These issues necessitate the development of highly convenient novel therapeutics with sufficient efficacy and fewer adverse effects [7].…”

Section: Introductionmentioning

confidence: 99%

Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats

Kiyohara¹,

Uta

Nagaoka³

et al. 2022

IJMS

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Several of the drugs currently available for the treatment of premature ejaculation (PE) (e.g., local anesthetics or antidepressants) are associated with numerous safety concerns and exhibit weak efficacy. To date, no therapeutics for PE have been approved in the United States, highlighting the need to develop novel agents with sufficient efficacy and fewer side effects. In this study, we focused on the histamine H3 receptor (H3R) as a potential target for the treatment of PE and evaluated the effects of imetit (an H3R/H4R agonist), ciproxifan (an H3R antagonist), and JNJ-7777120 (an H4R antagonist) in vivo. Our in vivo electrophysiological experiments revealed that imetit reduced mechanical stimuli-evoked neuronal firing in anesthetized rats. This effect was inhibited by ciproxifan but not by JNJ-7777120. Subsequently, we evaluated the effect of imetit using a copulatory behavior test to assess ejaculation latency (EL) in rats. Imetit prolonged EL, although this effect was inhibited by ciproxifan. These findings indicate that H3R stimulation suppresses mechanical stimuli-evoked neuronal firing in the spinal–penile neurotransmission system, thereby resulting in prolonged EL. To our knowledge, this is the first report to describe the relationship between H3R and PE. Thus, H3R agonists may represent a novel treatment option for PE.

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An update on the treatment of premature ejaculation: A systematic review

Cited by 15 publications

References 156 publications

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

6‐nitrodopamine is a major endogenous modulator of human vas deferens contractility

Selective serotonin reuptake inhibitors combined with traditional Chinese medicine for premature ejaculation: A systematic review and meta‐analysis

Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats

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