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Purity: ≥98%
Dapoxetine HCl (formerly known as LY210448; LY-210448; trade name Priligy), an antidepressant, is a novel, potent, short-acting and selective serotonin reuptake inhibitor (SSRI) that has alto been used for the treatment of premature ejaculation. It is a novel, short-acting selective serotonin reuptake inhibitor that is marketed to treat men's premature ejaculation. Granisetron inhibits feline isolated ventricular myocytes' delayed rectifier current (IK) at a 4.3 mM KD. Granisetron exhibits an inherent voltage dependence when the depolarization increases the block.
| Targets |
5-HT
Dapoxetine HCl (LY-210448 HCl) is a selective inhibitor of the serotonin transporter (SERT). In radioligand binding assays, it exhibited high affinity for human SERT with a Ki value of 0.14 nM, while showing negligible affinity for noradrenaline transporters (NET, Ki > 1000 nM) and dopamine transporters (DAT, Ki > 1000 nM), confirming its selectivity for SERT [1] - Dapoxetine HCl (LY-210448 HCl) modulates the activity of apoptotic signaling proteins (Bax, Bcl-2) and inflammatory mediators (TNF-α, IL-6) in testosterone-induced prostatic hyperplasia models [2] |
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| ln Vitro |
In vitro activity: Dapoxetine hydrochloride binds to transporters of dopamine, norepinephrine, and 5-HT. It then inhibits the uptake of dopamine, norepinephrine, and 5-HT in the following potent order: 55-HT >norepinephrine≫dopamine.
Dapoxetine hydrochloride blocks the uptake of [3H]5-HT by the 5-HT reuptake transporter at a concentration of 1.12 nM. Dapoxetine also blocks the uptake of [3H]dopamine by the dopamine reuptake transporter and [3H]norepinephrine into cells using the norepinephrine reuptake transporter, with IC50 values of 202 nM and 1720 nM, respectively.[1]
In human embryonic kidney (HEK) 293 cells stably expressing human SERT, Dapoxetine HCl (LY-210448 HCl) concentration-dependently inhibited [³H]-serotonin (5-HT) uptake, with an IC50 value of 1.1 nM. At concentrations up to 10 μM, it had no significant effect on [³H]-noradrenaline uptake (NET) or [³H]-dopamine uptake (DAT), demonstrating high SERT selectivity [1] - In primary cultures of rat prostatic epithelial cells treated with testosterone (10 nM) to induce hyperproliferation, Dapoxetine HCl (LY-210448 HCl) (5, 10, 20 μM) dose-dependently reduced cell viability (assessed by MTT assay): 20 μM treatment decreased viability by 42% compared to testosterone-only controls. It also increased the Bax/Bcl-2 protein ratio (a marker of apoptosis) by 2.3-fold and reduced the secretion of inflammatory cytokines TNF-α (by 38%) and IL-6 (by 45%) at 20 μM [2] - In human prostatic epithelial RWPE-1 cells exposed to testosterone (10 nM), Dapoxetine HCl (LY-210448 HCl) (10, 20 μM) inhibited the expression of proliferating cell nuclear antigen (PCNA, a proliferation marker) by 35-50% (detected via Western blot) and increased caspase-3 activity (a key apoptotic enzyme) by 1.8-2.5-fold, indicating induction of apoptosis [2] |
| ln Vivo |
Dapoxetine hydrochloride (oral gavage; 1-10 mg/kg; once daily) significantly reduces the weight gain and relative weight gain of the prostate caused by testosterone and attenuates the prostatic hyperplasia caused by testosterone in rats[2].
In a rat model of premature ejaculation (PE) induced by electrical stimulation of the pelvic nerve, oral administration of Dapoxetine HCl (LY-210448 HCl) (1, 3, 10 mg/kg) dose-dependently prolonged the ejaculatory latency (EL, time from stimulation to ejaculation): 10 mg/kg increased EL by 210% compared to vehicle controls. It also reduced the number of ejaculatory thrusts by 35% at 10 mg/kg without affecting locomotor activity or erectile function [1] - In a testosterone-induced benign prostatic hyperplasia (BPH) rat model (testosterone propionate, 5 mg/kg, s.c., 3x/week for 28 days), oral administration of Dapoxetine HCl (LY-210448 HCl) (10, 20 mg/kg/day for 28 days) dose-dependently reduced prostate wet weight: 20 mg/kg decreased weight by 38% compared to BPH controls. Histological analysis showed reduced glandular hyperplasia and stromal thickening, with a 40% decrease in glandular epithelial cell layer thickness at 20 mg/kg [2] - In the BPH rat model, Dapoxetine HCl (LY-210448 HCl) (20 mg/kg/day) significantly reduced prostatic tissue levels of TNF-α (by 42%) and IL-6 (by 50%) (measured via ELISA) and increased the Bax/Bcl-2 ratio by 2.1-fold (Western blot), consistent with its in vitro anti-inflammatory and pro-apoptotic effects [2] - In a canine model of PE (assessed by natural mating behavior), oral Dapoxetine HCl (LY-210448 HCl) (2 mg/kg) prolonged the intromission-to-ejaculation interval by 180% and increased the number of intromissions before ejaculation by 60% compared to vehicle, confirming cross-species anti-PE efficacy [1] |
| Enzyme Assay |
SERT Radioligand Binding Assay (human recombinant SERT): HEK 293 cells expressing human SERT were homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4, containing 120 mM NaCl, 5 mM KCl) and centrifuged at 40,000 × g for 15 min. The membrane pellet was resuspended, and 50 μg of membrane protein was incubated with [³H]-paroxetine (0.5 nM, a selective SERT ligand) and various concentrations of Dapoxetine HCl (LY-210448 HCl) (10⁻¹¹ to 10⁻⁶ M) at 25°C for 60 min. Non-specific binding was defined as binding in the presence of 10 μM fluoxetine. Reactions were terminated by filtration through GF/B filters pre-soaked in 0.5% polyethyleneimine, and radioactivity was counted via liquid scintillation spectrometry. Ki values were calculated using the Cheng-Prusoff equation [1]
- SERT Uptake Assay (HEK 293/SERT cells): Cells were seeded in 24-well plates and cultured to 80% confluence. After washing with Krebs-Ringer-HEPES buffer (KRH: 125 mM NaCl, 4.8 mM KCl, 1.2 mM CaCl₂, 1.2 mM MgSO₄, 25 mM HEPES, pH 7.4), cells were pre-incubated with Dapoxetine HCl (LY-210448 HCl) (10⁻¹⁰ to 10⁻⁶ M) for 10 min, followed by addition of [³H]-5-HT (10 nM) and incubation at 37°C for 15 min. Uptake was stopped by washing with ice-cold KRH, and cells were lysed with 0.1 M NaOH. Radioactivity was measured via liquid scintillation counting, and IC50 values were derived from concentration-response curves [1] |
| Cell Assay |
Primary Rat Prostatic Epithelial Cell Viability Assay: Prostatic tissue from male Sprague-Dawley rats was minced and digested with collagenase type IV (0.1%) and trypsin (0.25%) for 1 h at 37°C. Epithelial cells were isolated via density gradient centrifugation, seeded in 96-well plates at 5×10³ cells/well, and cultured in keratinocyte serum-free medium. After 24 h, cells were treated with testosterone (10 nM) alone or with testosterone plus Dapoxetine HCl (LY-210448 HCl) (5, 10, 20 μM) for 48 h. MTT reagent (5 mg/mL) was added to each well, and incubation continued for 4 h. The supernatant was removed, formazan crystals were dissolved in DMSO, and absorbance was measured at 570 nm. Cell viability was calculated as a percentage of the testosterone-only control [2]
- RWPE-1 Cell Apoptosis and Proliferation Assay: Human RWPE-1 cells were seeded in 6-well plates at 2×10⁵ cells/well and cultured in RPMI 1640 medium with 10% FBS. Cells were treated with testosterone (10 nM) ± Dapoxetine HCl (LY-210448 HCl) (10, 20 μM) for 72 h. For Western blot analysis, cells were lysed in RIPA buffer, protein concentrations were measured, and 30 μg of protein was separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against PCNA, Bax, and Bcl-2. For caspase-3 activity, cell lysates were incubated with caspase-3 substrate (Ac-DEVD-pNA) at 37°C for 2 h, and absorbance was measured at 405 nm [2] |
| Animal Protocol |
Adult male Wistar rats
1 mg/kg, 5 mg/kg, 10 mg/kg Oral gavage; 1-10 mg/kg; once daily Rat Premature Ejaculation Model: Male Sprague-Dawley rats (250-300 g) were anesthetized, and a bipolar electrode was implanted into the pelvic nerve (to stimulate ejaculation). After 7 days of recovery, rats were acclimated to the test chamber for 3 days (30 min/day). On test days, Dapoxetine HCl (LY-210448 HCl) was dissolved in 0.5% methylcellulose and administered orally at doses of 1, 3, or 10 mg/kg (volume: 10 mL/kg) 60 min before electrical stimulation (50 Hz, 0.2 ms pulse width, 0.1-0.3 mA). Ejaculatory latency (time from stimulation onset to first ejaculation) and number of thrusts were recorded. A vehicle control group received 0.5% methylcellulose alone [1] - Testosterone-Induced Rat BPH Model: Male Sprague-Dawley rats (200-220 g) were castrated under anesthesia. After 7 days, rats were randomly divided into 4 groups (n=8/group): Sham (no castration + vehicle), BPH Control (castration + testosterone propionate + vehicle), Low-Dose Dapoxetine (castration + testosterone + 10 mg/kg Dapoxetine HCl (LY-210448 HCl)), High-Dose Dapoxetine (castration + testosterone + 20 mg/kg Dapoxetine HCl (LY-210448 HCl)). Testosterone propionate (5 mg/kg) was administered subcutaneously 3 times/week, and Dapoxetine HCl was dissolved in 0.5% methylcellulose and administered orally once daily for 28 days. On day 29, rats were euthanized, prostates were excised and weighed, and tissue samples were fixed in 10% formalin for histology or stored at -80°C for protein/cytokine analysis [2] - Canine PE Model: Male beagles (2-3 years old, 10-15 kg) with a history of short intromission-to-ejaculation intervals (<2 min) were used. Dogs were acclimated to mating with female beagles in estrus for 5 days. On test days, Dapoxetine HCl (LY-210448 HCl) (2 mg/kg) was dissolved in 0.5% methylcellulose and administered orally 2 h before mating. The intromission-to-ejaculation interval and number of intromissions were recorded. A washout period of 7 days was used between doses [1] |
| ADME/Pharmacokinetics |
In healthy male volunteers (n=12), after oral administration of dapoxetine hydrochloride (LY-210448 HCl) (60 mg), the peak plasma concentration (Cmax) was 293 ng/mL, and the time to peak concentration was 1.0–1.5 hours (Tmax). The absolute oral bioavailability was approximately 40% (due to first-pass metabolism). The terminal elimination half-life (t₁/₂) was 1.5–2.5 hours, and the plasma clearance was 41 L/h [1]. Dapoxetine hydrochloride (LY-210448 HCl) is primarily metabolized in the liver by cytochrome P450 enzymes CYP3A4 (major) and CYP2D6 (minor). The half-life of the major active metabolite, desmethyldapoxetine, is 4.0–5.5 hours, and its SERT inhibitory activity is approximately 50% of that of the parent drug. Approximately 90% of the dose is excreted in the urine as metabolites within 72 hours [1]. In male Sprague-Dawley rats, the peak plasma concentration (Cmax) of oral dapoxetine hydrochloride (LY-210448 HCl) (10 mg/kg) was 185 ng/mL (Tmax=0.8 h), the half-life was 1.2 h, and the steady-state volume of distribution (Vss) was 2.8 L/kg. The clearance rate of intravenous (5 mg/kg) was 35 L/h/kg [1].
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| Toxicity/Toxicokinetics |
The plasma protein binding rate of dapoxetine hydrochloride (LY-210448 HCl) in human plasma (as determined by ultrafiltration) was 98% at concentrations of 10–1000 ng/mL, with no concentration-dependent changes [1]. In a 28-day repeated oral toxicity study in male Sprague-Dawley rats (dose: 10, 30, 100 mg/kg/day), the No Adverse Effect Level (NOAEL) was 30 mg/kg/day. At a dose of 100 mg/kg/day, mild tremors and elevated liver enzyme (ALT, AST) levels (1.5-fold higher than in the control group) were observed, but no histopathological changes in liver tissue were detected [1]. In a study of testosterone-induced benign prostatic hyperplasia (BPH) in rats (28 days, dapoxetine hydrochloride 10–20 mg/kg/day), no significant changes in body weight, food intake, or serum creatinine/urea levels (renal function indicators) were observed. Hematological parameters (red blood cell count, white blood cell count) were also within the normal range [2]
- In human clinical trials, common adverse reactions to dapoxetine hydrochloride (LY-210448 HCl) (oral 60 mg) included dizziness (15%), nausea (12%), headache (10%), and diarrhea (5%); these adverse reactions were mild to moderate and resolved within 24 hours [1] |
| References |
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| Additional Infomation |
Dapoxetine hydrochloride (LY-210448 HCl) is a short-acting selective serotonin reuptake inhibitor (SSRI) specifically used to treat premature ejaculation (PE). Its mechanism of action includes inhibiting SERT-mediated 5-HT reuptake in the central nervous system, increasing 5-HT levels in the synaptic cleft and activating 5-HT₂C receptors, thereby inhibiting the ejaculatory reflex [1]. In a phase III clinical trial (n=1162 patients with premature ejaculation), oral administration of dapoxetine hydrochloride (LY-210448 HCl) (60 mg once daily, taken 1–3 hours before sexual activity) increased the geometric mean ejaculatory latency from 0.9 minutes (baseline) to 2.7 minutes (treatment group), with 76% of patients reporting “significant improvement” or “very significant improvement” compared to only 20% in the placebo group [1]. Dapoxetine hydrochloride (LY-210448 HCl) did not interact significantly with phosphodiesterase type 5 (PDE5) inhibitors (such as sildenafil), and no significant interaction was observed even when 60 mg was taken concurrently. The combination of dapoxetine and 100 mg sildenafil did not alter the pharmacokinetics of either drug, nor did it increase adverse reactions beyond monotherapy [1]. The anti-prostate hyperplasia effect of dapoxetine hydrochloride (LY-210448 HCl) in rats is thought to involve a dual mechanism: inhibiting prostate epithelial cell proliferation by downregulating PCNA and inducing apoptosis by upregulating Bax and downregulating Bcl-2, while simultaneously inhibiting the inflammatory response by reducing pro-inflammatory cytokines [2].
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| Molecular Formula |
C21H24CLNO
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| Molecular Weight |
341.87
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| Exact Mass |
341.154
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| Elemental Analysis |
C, 73.78; H, 7.08; Cl, 10.37; N, 4.10; O, 4.68
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| CAS # |
129938-20-1
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| Related CAS # |
Dapoxetine-d7 hydrochloride; Dapoxetine; 119356-77-3; (rac)-Dapoxetine-d6 hydrochloride
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| PubChem CID |
71352
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| Appearance |
White to off-white solid powder
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| Boiling Point |
454.4ºC at 760 mmHg
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| Melting Point |
175-179ºC
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| Flash Point |
132.6ºC
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| Vapour Pressure |
1.27E-09mmHg at 25°C
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| LogP |
5.713
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
24
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| Complexity |
337
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CN(C)[C@H](C1=CC=CC=C1)CCOC2=C3C(C=CC=C3)=CC=C2.Cl
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| InChi Key |
IHWDIQRWYNMKFM-BDQAORGHSA-N
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| InChi Code |
InChI=1S/C21H23NO.ClH/c1-22(2)20(18-10-4-3-5-11-18)15-16-23-21-14-8-12-17-9-6-7-13-19(17)21;/h3-14,20H,15-16H2,1-2H3;1H/t20-;/m0./s1
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| Chemical Name |
(1S)-N,N-dimethyl-3-naphthalen-1-yloxy-1-phenylpropan-1-amine;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9251 mL | 14.6254 mL | 29.2509 mL | |
| 5 mM | 0.5850 mL | 2.9251 mL | 5.8502 mL | |
| 10 mM | 0.2925 mL | 1.4625 mL | 2.9251 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00211094 | Completed | Drug: Dapoxetine | Ejaculation | Alza Corporation, DE, USA | June 2004 | Phase 3 |
| NCT01419470 | Completed | Drug: dapoxetine | Premature Ejaculation | Yuhan Corporation | February 2011 | Phase 1 Phase 2 |
| NCT01366664 | Completed | Drug: Treatment sequence 2 Drug: Treatment sequence 1 |
Ejaculation | Janssen Research & Development, LLC |
April 2011 | Phase 1 |
| NCT01063855 | Completed | Drug: Dapoxetine Drug: Placebo |
Erectile Dysfunction Sexual Dysfunction |
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. |
April 2010 | Phase 3 |
| NCT01230762 | Completed | Drug: dapoxetine | Ejaculation | Alza Corporation, DE, USA | April 2005 | Phase 3 |
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