Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins

"Discontinuation of Dapoxetine Treatment in Patients With Premature Ejaculation: A 2-Year Prospective Observational Study". "Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction". "Dapoxetine-A Novel Drug for Premature Ejaculation".

Conflict of interest

"Dapoxetine has long-term efficacy in the treatment of premature ejaculation". "AUA guideline on the pharmacologic management of premature ejaculation". "Dapoxetine: An Innovative Approach in the Therapeutic Management In Animal Model of Depression". "Antistress and antidepressant properties of dapoxetine and vortioxetine". "Dapoxetine for the treatment of premature ejaculation: results from a randomized, double-blind, placebo-controlled phase 3 trial in 22 countries". "Dapoxetine for the treatment of premature ejaculation: Lack of interaction with ethanol". "Monoaminergic transporter binding and inhibition profile of dapoxetine, a medication for the treatment of premature ejaculation". "Physiology of ejaculation: emphasis on serotonergic control". "Supraspinal site of action for the inhibition of ejaculatory reflex by dapoxetine". "Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials". ^ "Dapoxetine: a guide to its use in premature ejaculation". "Pharmacokinetics of single and multiple escalating doses of dapoxetine in healthy volunteers". "Cardiovascular safety profile of dapoxetine during the premarketing evaluation". "Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of dapoxetine tadalafil tablets FDA reports".

"Selective serotonin reuptake inhibitor discontinuation syndrome: a review". "Emerging treatments for premature ejaculation: focus on dapoxetine".

• Dapoxetine 5mg works by increasing serotonin levels in the brain.
• It is recommended for men aged 18-64 suffering from early ejaculation.
• Dapoxetine is available by prescription only in many countries.
• Medication should be taken with a full glass of water.
• Avoid alcohol when using dapoxetine due to interactions.
• Dapoxetine may cause dizziness; avoid driving after taking it.
• Store dapoxetine in a cool, dry place away from children.

"Dapoxetine: a novel treatment for premature ejaculation".

• Dose adjustment may be necessary
• Reduced clearance in renal failure
• Monitor for increased side effects
• Lower starting dose recommended
• Consult a nephrologist if needed
• Risk of drug accumulation
• Watch for dizziness and falls
• Adjust frequency of dosing
• Do not exceed recommended limit
• Safety data is limited in renal impairment
• Adjust based on glomerular filtration rate
• Use with caution in moderate impairment

"Stereoselective synthesis of (S)-dapoxetine starting from trans-cinnamyl alcohol". "Medical Non-Endocrine-Targeted Therapies: Ejaculatory Dysfunction and Immunotherapy". Potent Selective serotonin reuptake inhibitor (SSRI); used in treatment of premature ejaculation Dapoxetine is capable of blocking recombinant Kv4.3 potassium voltage-gated channels. This compound is featured on the Biogenic Amine Transporters page of the Handbook of Receptor Classification and Signal Transduction. To browse other handbook pages, click here. This compound was developed by Eli Lilly. To browse the list of other pharma-developed compounds and Approved Drugs/Drug Candidates, click here. 4 Oral - Aquatic Chronic 4 - Eye Irrit.2 Choose from one of the most recent versions: Find documentation for the products that you have recently purchased in the Document Library. Check access to the full text by signing in through your organization. et al.Androgen receptor roles in the development of benign prostate hyperplasiaAm.J. et al.Adverse side effects of 5alpha-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patientsJ. et al.Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive reviewProg. et al.Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expressionEur. A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression?Neuropharmacology(2013) et al.Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in ratsToxicol.

et al.Influence of acrylamide on the gastric mucosa of adult albino rats and the possible protective role of rosemaryTissue Cell(2015) et al.Programmed cell death in animal development and diseaseCell(2011) Amelioration of testosterone-induced benign prostatic hyperplasia using febuxostat in rats: The role of VEGF/TGFβ and iNOS/COX-22020, European Journal of PharmacologyCitation Excerpt :In patients with BPH, the symptom score and prostate volume were significantly higher in patients with high-grade prostatic inflammation (Robert et al., 2009).

Tolerability and acute toxicity studies

Archived from the original on 2023-08-03. "Dapoxetine, a novel treatment for premature ejaculation, does not have pharmacokinetic interactions with phosphodiesterase-5 inhibitors". "Dapoxetine: a new option in the medical management of premature ejaculation". ^ "Priligy is used to Treat Premature Ejaculation". ^ a b c "Australian Public Assessment Report for Dapoxetine" (PDF).

Am. J. Pathol.

"Pharmacokinetic and pharmacodynamic features of dapoxetine, a novel drug for 'on-demand' treatment of premature ejaculation". "Dapoxetine: an evidence-based review of its effectiveness in treatment of premature ejaculation". ^ "Furiex Pharma gets rights to Priligy, some of which it sells on to Menarini". "New agents in the treatment of premature ejaculation". "Efficacy and tolerability of dapoxetine in treatment of premature ejaculation: an integrated analysis of two double-blind, randomised controlled trials". Experimentally, several studies have reported that testosterone-induced BPH is mediated by inflammation and that protective agents have anti-inflammatory properties (Atawia et al., 2014; Sayed et al., 2016).

• The medication is effective for many men but not all.
• Dapoxetine 5mg has a quick onset but short duration of action.
• It’s important to adhere to prescribed timing before sexual activity.
• Avoid combining with other serotonergic drugs without doctor’s approval.
• Keep track of any adverse reactions during therapy.
• Discuss potential interactions with other health products.
• Proper storage ensures the medicine’s effectiveness over time.

In the present study, testosterone significantly increased the levels of TNF-α and IL-6 in the prostate. In patients with BPH, the symptom score and prostate volume were significantly higher in patients with high-grade prostatic inflammation (Robert et al., 2009). Chronic inflammation may contribute to tissue injury, directly through activating cytokines release and increasing the concentration of growth factors (Sayed et al., 2016).

Rights and permissions

Dapoxetine is metabolized extensively in the liver and kidney by multiple enzymes such as CYP2D6, CYP3A4, and flavin monooxygenase 1. The major product at the end of the metabolic pathway is circulating dapoxetine N-oxide, which is a weak SSRI and contributes no clinical effect. The metabolites of dapoxetine are eliminated rapidly in the urine with a terminal half-life of 18.7 and 21.9 hours for a single dose of 30 mg and 60 mg, respectively. The cardiovascular safety profile of dapoxetine has been studied extensively during the drug development. Phase I trials showed that dapoxetine had neither clinically significant electrocardiographic effects nor delayed repolarization effects, with dosing up to four-fold greater than the maximum recommended dosage, which is 60 mg.

Particle morphology

Phase III studies in men with PE showed a safety and well tolerated profile of dapoxetine with dosing of 30 and 60 mg. No cardiovascular adverse had been found. Studies of SSRIs in patients with major psychiatric disorders prove that SSRIs are potentially associated with certain neurocognitive adverse effects such as anxiety, akathisia, hypomania, changes in mood, or suicidal thought. [30][31] No study on the effects of SSRIs in men with PE has been done. McMahon's study in 2012 showed that dapoxetine has no effect on mood and is not associated with anxiety or suicidality.

Ethics approval and consent to participate

The incidence of antidepressant discontinuation syndrome symptoms in men using dapoxetine to treat PE has been described by reviewers as low or no different from the incidence of such symptoms in men withdrawn from placebo treatment. [33][34] The lack of chronic serotonergic stimulation with on-demand dapoxetine minimizes the potentiation action of serotonin at synaptic cleft, thus decreasing the risk of discontinuation symptoms. Currently, very few methods are used to synthesize (S)-dapoxetine. This novel approach consists of only six steps in which three main steps are shown above. The initial reactant is trans-cinnamyl alcohol, which is commercially available. Accumulating evidence also indicates that the pathogenesis of BPH depends on angiogenesis (Lin et al., 2014). This is evidenced by the histological inflammation in BPH specimens and chronically activated T cells and macrophages associated with BPH nodules (Nickel, 2008).

About dapoxetine

Sharpless asymmetric epoxidation and Mitsunobu reaction have been used to produce expected (S)-dapoxetine. This method is considered a good choice compared to the known methods due to high yield and easily obtainable reactants. Dapoxetine was created by Eli Lilly and in phase I clinical trial as an antidepressant. It never worked out well as a medication for the treatment of depression, though, and was shelved for a while before subsequently developed to treat PE. In December 2003, Eli Lilly sold the patent for dapoxetine to Pharmaceutical Product Development (PPD) for US$65 million.

Graphical Abstract

Eli Lilly may also receive royalties payment from PPD if the sale exceeds a certain amount. Research into the effectiveness of dapoxetine was revisited in 2020. ALZA is the current owner of dapoxetine, but PPD will receive milestone payments and drug royalties from ALZA. If approved, dapoxetine will be marketed in the US by Ortho McNeil pharmaceutical, Inc. Ortho McNeil and dapoxetine over counter Janssen-Ortho Inc, or Janssen-Cilag are all units of Johnson & Johnson.

STORAGE & DOSAGE:

As at 2005, dapoxetine was in phase III clinical trials, pending review by the FDA. Dapoxetine has been marketed and approved in more than 50 countries. [39] Dapoxetine has been approved in Italy, Spain, Mexico, South Korea, and New Zealand in 2009 and 2010; marketed in Sweden, Austria, Germany, Finland, Spain, Portugal, and Italy. It has also been approved in France, Russia, Malaysia, Philippines, Argentina, and Uruguay. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). The sub formula of Dapoxetine is C21H23NO, white to off-white crystalline powder, molecular weight is 305.413, density is 1.081 g/cm³, CAS number is 119356-77-3, it can rapidly act and metabolize selective serotonin reabsorption Inhibitors (SSRIs), indicated for the treatment of premature ejaculation in men[1].

• Use of dapoxetine 5mg may require dose adjustment over time.
• Erectile function is unaffected directly by dapoxetine.
• If a dose is missed, take it as soon as remembered.
• Do not double doses to compensate for missed ones.
• Potential for abnormal bleeding exists; inform your doctor.
• Step-by-step adherence ensures safe and effective use.
• Medical consultation should occur before any change in regimen.