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]

达泊西汀不仅降低Kv4.3电流的峰值幅度，而且以浓度依赖性方式加速电流失活的衰减速率。达泊西汀降低去极化脉冲持续时间内 Kv4.3 电流的积分，IC50 为 5.3 μM。达泊西汀还会导致封闭状态失活的显着加速。达泊西汀产生显着的使用依赖性阻断，并伴随着 Kv4.3 电流失活的延迟恢复。达泊西汀以浓度依赖性方式降低 Kv1.5 电流的峰值幅度并加速电流失活的衰减速率，IC50 为 11.6 μM。达泊西汀降低尾电流幅度并减缓 Kv1.5 的失活过程，从而导致尾交叉现象。达泊西汀在 1 和 2 Hz 频率下产生依赖于使用的 Kv1.5 阻断，并减慢失活恢复的时间过程。达泊西汀似乎也是吗啡的有用辅助剂，可降低镇痛阈值，尽管达泊西汀本身的镇痛活性可以忽略不计。达泊西汀是 LY 243917 的 D-对映体，作为血清素再摄取抑制剂的效力是 L-对映体的 3.5 倍。

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在稳定表达人SERT的人胚胎肾（HEK）293细胞中，Dapoxetine HCl (LY-210448 HCl) 可浓度依赖性地抑制[³H]-5-羟色胺（5-HT）摄取，IC50值为1.1 nM。在浓度高达10 μM时，其对[³H]-去甲肾上腺素摄取（NET介导）或[³H]-多巴胺摄取（DAT介导）无显著影响，体现出高SERT选择性[1]
- 在经睾酮（10 nM）诱导过度增殖的大鼠原代前列腺上皮细胞中，Dapoxetine HCl (LY-210448 HCl)（5、10、20 μM）可剂量依赖性降低细胞活力（MTT法检测）：20 μM处理组的细胞活力较仅睾酮处理组降低42%。同时，20 μM剂量可使凋亡标志物Bax/Bcl-2蛋白比值升高2.3倍，并减少炎症因子TNF-α（降低38%）和IL-6（降低45%）的分泌[2]
- 在经睾酮（10 nM）处理的人前列腺上皮RWPE-1细胞中，Dapoxetine HCl (LY-210448 HCl)（10、20 μM）可使增殖标志物增殖细胞核抗原（PCNA）的表达降低35%-50%（Western blot检测），并使关键凋亡酶caspase-3的活性升高1.8-2.5倍，表明其可诱导细胞凋亡[2]

盐酸达泊西汀（口服灌胃；1-10 mg/kg；每日一次）可显着降低大鼠睾酮引起的前列腺体重增加和相对体重增加，并减轻睾酮引起的前列腺增生[2]。

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在盆腔神经电刺激诱导的大鼠早泄（PE）模型中，口服Dapoxetine HCl (LY-210448 HCl)（1、3、10 mg/kg）可剂量依赖性延长射精潜伏期（EL，从刺激开始到首次射精的时间）：10 mg/kg剂量较溶媒对照组使EL延长210%。同时，10 mg/kg剂量可使射精推力次数减少35%，且不影响自发活动或勃起功能[1]
- 在睾酮诱导的大鼠良性前列腺增生（BPH）模型中（丙酸睾酮5 mg/kg，皮下注射，每周3次，持续28天），口服Dapoxetine HCl (LY-210448 HCl)（10、20 mg/kg/天，持续28天）可剂量依赖性降低前列腺湿重：20 mg/kg剂量较BPH对照组使重量降低38%。组织学分析显示，腺体增生和间质增厚程度减轻，20 mg/kg剂量使腺上皮细胞层厚度降低40%[2]
- 在BPH大鼠模型中，Dapoxetine HCl (LY-210448 HCl)（20 mg/kg/天）可显著降低前列腺组织中TNF-α（降低42%）和IL-6（降低50%）的水平（ELISA检测），并使Bax/Bcl-2比值升高2.1倍（Western blot检测），与其体外抗炎和促凋亡作用一致[2]
- 在犬早泄模型中（通过自然交配行为评估），口服Dapoxetine HCl (LY-210448 HCl)（2 mg/kg）较溶媒对照组使插入-射精间隔延长180%，并使射精前插入次数增加60%，证实其跨物种的抗早泄疗效[1]

SERT放射性配体结合实验（人重组SERT）：将表达人SERT的HEK 293细胞在冰浴的Tris-HCl缓冲液（50 mM，pH 7.4，含120 mM NaCl、5 mM KCl）中匀浆，40,000 × g离心15 min。重悬膜沉淀后，取50 μg膜蛋白与[³H]-帕罗西汀（0.5 nM，选择性SERT配体）及不同浓度的Dapoxetine HCl (LY-210448 HCl)（10⁻¹¹-10⁻⁶ M）在25°C孵育60 min。非特异性结合定义为在10 μM氟西汀存在下的结合。反应通过预浸泡于0.5%聚乙烯亚胺的GF/B滤膜过滤终止，采用液体闪烁光谱法计数放射性。利用Cheng-Prusoff方程计算Ki值[1]
- SERT摄取实验（HEK 293/SERT细胞）：将细胞接种于24孔板，培养至80%汇合度。用Krebs-Ringer-HEPES缓冲液（KRH：125 mM NaCl、4.8 mM KCl、1.2 mM CaCl₂、1.2 mM MgSO₄、25 mM HEPES，pH 7.4）洗涤后，细胞与Dapoxetine HCl (LY-210448 HCl)（10⁻¹⁰-10⁻⁶ M）预孵育10 min，随后加入[³H]-5-HT（10 nM），37°C孵育15 min。通过冰浴KRH洗涤终止摄取，用0.1 M NaOH裂解细胞。采用液体闪烁计数法检测放射性，通过浓度-效应曲线推导IC50值[1]

大鼠原代前列腺上皮细胞活力实验：将雄性Sprague-Dawley大鼠的前列腺组织切碎，用IV型胶原酶（0.1%）和胰蛋白酶（0.25%）在37°C消化1 h。通过密度梯度离心分离上皮细胞，以5×10³个细胞/孔接种于96孔板，用角质形成细胞无血清培养基培养。24 h后，细胞分别用仅睾酮（10 nM）或睾酮+Dapoxetine HCl (LY-210448 HCl)（5、10、20 μM）处理48 h。向各孔加入MTT试剂（5 mg/mL），继续孵育4 h。去除上清液，用DMSO溶解甲瓒结晶，在570 nm处测定吸光度。细胞活力以仅睾酮处理组为对照计算百分比[2]
- RWPE-1细胞凋亡与增殖实验：将人RWPE-1细胞以2×10⁵个细胞/孔接种于6孔板，用含10%胎牛血清的RPMI 1640培养基培养。细胞用睾酮（10 nM）±Dapoxetine HCl (LY-210448 HCl)（10、20 μM）处理72 h。Western blot分析时，用RIPA缓冲液裂解细胞，测定蛋白浓度后，取30 μg蛋白进行SDS-PAGE电泳，转移至PVDF膜，用PCNA、Bax和Bcl-2抗体孵育检测。检测caspase-3活性时，将细胞裂解液与caspase-3底物（Ac-DEVD-pNA）在37°C孵育2 h，在405 nm处测定吸光度[2]

Adult male Wistar rats
1 mg/kg, 5 mg/kg, 10 mg/kg
Oral gavage; 1-10 mg/kg; once daily

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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]

In healthy male volunteers (n=12), oral administration of Dapoxetine HCl (LY-210448 HCl) (60 mg) showed a peak plasma concentration (Cmax) of 293 ng/mL at 1.0-1.5 h (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 h, and plasma clearance was 41 L/h [1]
- Dapoxetine HCl (LY-210448 HCl) is primarily metabolized in the liver by cytochrome P450 enzymes CYP3A4 (major) and CYP2D6 (minor). The main active metabolite, desmethyl dapoxetine, has a t₁/₂ of 4.0-5.5 h and exhibits 50% of the SERT inhibitory activity of the parent drug. Approximately 90% of the dose is excreted in urine (as metabolites) within 72 h [1]
- In male Sprague-Dawley rats, oral Dapoxetine HCl (LY-210448 HCl) (10 mg/kg) had a Cmax of 185 ng/mL (Tmax=0.8 h), t₁/₂ of 1.2 h, and volume of distribution at steady state (Vss) of 2.8 L/kg. Intravenous administration (5 mg/kg) showed a clearance of 35 L/h/kg [1]

The plasma protein binding rate of Dapoxetine HCl (LY-210448 HCl) in human plasma (measured via 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 (doses: 10, 30, 100 mg/kg/day), the no-observed-adverse-effect level (NOAEL) was 30 mg/kg/day. At 100 mg/kg/day, mild tremors and increased liver enzyme (ALT, AST) levels (1.5-fold vs. control) were observed, but no histopathological changes in the liver were detected [1]
- In the testosterone-induced BPH rat study (28 days, 10-20 mg/kg/day Dapoxetine HCl), no significant changes in body weight, food intake, or serum creatinine/urea levels (kidney function markers) were observed. Hematology parameters (red blood cell count, white blood cell count) were also within normal ranges [2]
- In human clinical trials, common adverse effects of Dapoxetine HCl (LY-210448 HCl) (60 mg oral) included dizziness (15%), nausea (12%), headache (10%), and diarrhea (5%); these effects were mild to moderate and resolved within 24 h [1]

[1]. Dapoxetine, a novel selective serotonin transport inhibitor for the treatment of premature ejaculation. Ther Clin Risk Manag. 2007 Jun;3(2):277-89.

[2]. Dapoxetine attenuates testosterone-induced prostatic hyperplasia in rats by the regulation of inflammatory and apoptotic proteins. Toxicol Appl Pharmacol. 2016 Nov 15;311:52-60.

Dapoxetine HCl (LY-210448 HCl) is a short-acting, selective serotonin reuptake inhibitor (SSRI) specifically developed for the treatment of premature ejaculation (PE). Its mechanism of action involves inhibiting SERT-mediated reuptake of 5-HT in the central nervous system, increasing synaptic 5-HT levels and activating 5-HT₂C receptors, which suppress the ejaculatory reflex [1]
- In a phase III clinical trial (n=1162 PE patients), oral Dapoxetine HCl (LY-210448 HCl) (60 mg once daily 1-3 h before sexual activity) increased the geometric mean ejaculatory latency from 0.9 min (baseline) to 2.7 min (treatment), with 76% of patients reporting a "much improved" or "very much improved" condition vs. 20% in the placebo group [1]
- Dapoxetine HCl (LY-210448 HCl) exhibits no significant interaction with phosphodiesterase type 5 (PDE5) inhibitors (e.g., sildenafil), as co-administration of 60 mg dapoxetine and 100 mg sildenafil did not alter the pharmacokinetics of either drug or increase adverse effects beyond those of monotherapy [1]
- The anti-prostatic hyperplasia effect of Dapoxetine HCl (LY-210448 HCl) in rats is thought to involve dual mechanisms: inhibition of prostatic epithelial cell proliferation via downregulating PCNA, and induction of apoptosis via upregulating Bax and downregulating Bcl-2, alongside suppression of inflammatory responses by reducing pro-inflammatory cytokines [2]

C21H24CLNO

341.87

341.154

C, 73.78; H, 7.08; Cl, 10.37; N, 4.10; O, 4.68

129938-20-1

Dapoxetine-d7 hydrochloride; Dapoxetine; 119356-77-3; (rac)-Dapoxetine-d6 hydrochloride

71352

White to off-white solid powder

454.4ºC at 760 mmHg

175-179ºC

132.6ºC

1.27E-09mmHg at 25°C

5.713

12.47

1

2

6

24

337

1

CN(C)[C@H](C1=CC=CC=C1)CCOC2=C3C(C=CC=C3)=CC=C2.Cl

IHWDIQRWYNMKFM-BDQAORGHSA-N

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

(1S)-N,N-dimethyl-3-naphthalen-1-yloxy-1-phenylpropan-1-amine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。