Paroxetine hydrochloride hemihydrate (BRL29060 hydrochloride hemihydrate)
(Synonyms: 盐酸帕罗西汀半水合物; BRL29060 hydrochloride hemihydrate; BRL29060A hemihydrate) 目录号 : GC30992
Paroxetine HCl (BRL-29060A, FG-7051) is an antidepressant drug of the SSRI type.
Cas No.:110429-35-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Cell viability is determined by the tetrazolium salt 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. BV2 and primary microglial cells are initially seeded into 96-well plates at a density of 1×104 cells/well and 5×104 cells/well, respectively. Following treatment, MTT (5 mg/mL in PBS) is added to each well and incubated at 37°C for four hours. The resulting formazan crystals are dissolved in dimethylsulfoxide (DMSO). The optical density is measured at 570 nm, and results are expressed as a percentage of surviving cells compared with the control. |
Animal experiment: | Animals are divided into two main groups: 1) pre-emptive and 2) post-injury group. Each main group is divided into three different subgroups: I) CCI vehicle-treated group, II) sham group, and III) CCI paroxetine-treated group. Vehicle is injected i.p. to CCI and sham-operated animals. In the pre-emptive study, paroxetine (10 mg/kg) is injected 1 h before surgery and continued daily until day 14 post surgery. In the post-injury group, paroxetine (10 mg/kg) is administered at day 7 post injury and continued daily until day 14. All behavioral tests are recorded on day 0 (control day) before surgery and on days 1, 3, 5, 7, 10, and 14 post-nerve injury. |
References: [1]. Wang Q, et al. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364. | |
Paroxetine HCl (BRL-29060A, FG-7051) is an antidepressant drug of the SSRI type.
Paroxetine apparently exerts their antidepressant activity by increasing the concentration of 5-HT in the extracellular compartment, thereby enhancing serotoninergic neurotransmission. Paroxetine (1-300 μM) results in a concentration-dependent reduction in the firing rate of DRN serotoninergic neurons with IC50 values of 1.4 μM in the ACSF superfusing brain stem slices. [1] Paroxetine is a highly potent inhibitor of desipramine hydroxylation, the inhibition constant (Ki) value of 2.0 mM indicated greater inhibiting potency than fluoxetine or norfluoxetine. [2] Paroxetine is shown to be a potent (Ki = 1.1 nM) and specific inhibitor of [3H]-5-hydroxytryptamine (5-HT) uptake into rat cortical and hypothalamic synaptosomes in vitro. Paroxetine demonstrates weak affinity for muscarinic receptors (Ki = 89 nM) but is at least 15 fold weaker than amitriptyline (Ki = 5.1 nM). [3] Paroxetine inactivates CYP2D6 via the formation of a metabolite intermediate complex. [4]
Paroxetine produces a dose-related inhibition of [3H]-5-HT uptake (ED50 = 1.9 mg/kg) into rat hypothalamic synaptosomes ex vivo with little effect on [3H]-l-noradrenaline (NA) uptake (ED50 greater than 30 mg/kg). Paroxetine (ED50 1-3 mg/kg PO) prevents the 5-HT depleting effect of p-chloroamphetamine (PCA) in rat brain, demonstrating 5-HT uptake blockade in vivo. [3]
[1] Le Poul E, et al. Naunyn Schmiedebergs Arch Pharmacol, 1995, 352(2), 141-148. [2] von Moltke LL, et al. J Clin Psychopharmacol, 1995, 15(2), 125-131. [3] Thomas DR, et al. Psychopharmacology (Berl), 1987, 93(2), 193-200.
| Cas No. | 110429-35-1 | SDF | |
| 别名 | 盐酸帕罗西汀半水合物; BRL29060 hydrochloride hemihydrate; BRL29060A hemihydrate | ||
| Canonical SMILES | FC1=CC=C([C@H]2[C@H](COC3=CC=C(OCO4)C4=C3)CNCC2)C=C1.[0.5H2O].Cl | ||
| 分子式 | C19H22ClFNO3.5 | 分子量 | 374.83 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6679 mL | 13.3394 mL | 26.6788 mL |
| 5 mM | 0.5336 mL | 2.6679 mL | 5.3358 mL |
| 10 mM | 0.2668 mL | 1.3339 mL | 2.6679 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Paroxetine hydrochloride hemihydrate
The structure of the title compound {systematic name: (3S-trans)-3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4- fluorophenyl)piperidinium chloride hemihydrate, C19H21FNO3+.Cl-.0.5H2O}, comprises two piperidinium cations (A and B), two chloride anions, and one water molecule in the asymmetric unit. A piperidinium proton of cation A is hydrogen bonded to the water molecule. The second proton points in the direction of one chloride anion, as does a piperidinium proton of cation B. One water proton points in the direction of another chloride anion.
Premature ejaculation: definition and drug treatment
Premature ejaculation (PE) is a frequent male sexual complaint that is mediated mainly by disturbances of serotonergic neurotransmission and certain serotonin (5-HT) receptors and, to a lesser extent, oxytocinergic neurotransmission in the CNS. The current Diagnostic Manual of Mental Disorders (fourth edition, revised text) [DSM-IV-TR] definition of PE has a low positive predictive value and is inadequate for clinical, epidemiological and drug treatment research. Categorisation of PE into four well defined syndromes has recently been proposed for the pending DSM (fifth edition) definition of PE. Over the last decade, an increasing number of studies of drug treatment of PE have been published. A meta-analysis of those studies, conducted in accordance with current standards of evidence-based medicine, demonstrated similar efficacies for daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline and fluoxetine, with paroxetine (hydrochloride) hemihydrate exerting the strongest effect on ejaculation. On the basis of fundamental insights into serotonergic neurotransmission, it has been suggested that on-demand selective serotonin reuptake inhibitor (SSRI) treatment will not lead to similarly impressive delays in ejaculation as has been observed with daily SSRI treatment. Indeed, some on-demand studies with SSRIs and studies with the new SSRI dapoxetine have shown a weak ejaculation-delaying effect after 1-2 hours of drug intake. Apart from daily treatment with SSRIs, PE can be delayed by on-demand use of topical anaesthetics and tramadol. Treatment with phosphodiesterase type 5 inhibitors should not be prescribed to men with PE with normal erectile function, but may be used if PE is accompanied by erectile difficulties. There is no scientific support for treatment of PE with intracavernous injection of vasoactive drugs. Animal studies have shown that strong immediate ejaculation delay may be induced by administration of a combination of an SSRI with a serotonin 5-HT(1A) receptor antagonist. The combination of an SSRI and any other compound that immediately and potently raises serotonin neurotransmission and/or use of oxytocin receptor antagonists may form the basis for the development of new on-demand and/or daily drugs for the treatment of PE.
(3S,4R)-4-(4-Fluoro-phen-yl)-3-(hydroxy-meth-yl)piperidinium chloride
The title compound, C(12)H(17)FNO(+)·Cl(-), is a degradation impurity of paroxetine hydro-chloride hemihydrate (PAXIL), an anti-depressant belonging to the group of drugs called selective serotonin reuptake inhibitors (SSRIs). Similar to the paroxetine hydro-chloride salt with protonation having taken place on the basic piperidine ring, the degradation impurity also exists as the hydro-chloride salt. The cyclic six-membered piperidinium ring adopts a chair conformation with the hydroxy-methyl and 4-fluoro-phenyl groups in the equatorial positions. The ions form a tape along the b axis through charge-assisted N(+)-H?Cl(-) hydrogen bonds; these tapes are connected by O-H?Cl(-) hydrogen bonds along the a axis.
Development and comparative evaluation of in vitro, in vivo properties of novel controlled release compositions of paroxetine hydrochloride hemihydrate as against Geomatrix? platform technology
The objective of this study is to develop, in vitro and in vivo evaluation of novel approaches for controlled release of paroxetine hydrochloride hemihydrate (PHH) in comparison to patented formulation PAXIL CR(?) tablets of GlaxoSmithKline (Geomatrix? technology). In one of the approaches, hydrophilic core matrix tablets containing 85% of the dose were prepared and further coated with methacrylic acid copolymer to delay the release. An immediate release coating of 15% was given as top coat. The tablets were further optionally coated using ethyl cellulose. In the second approach, hydrophobic matrix core tablets containing metharylic acid copolymer were prepared. In the third approach, PHH was granulated with enteric polymer and further hydrophobic matrix core tablets were prepared. The effect of polymer concentration, level of enteric coating on drug release was evaluated by in vitro dissolution study by varying dissolution apparatus and the rotation speeds. It was found that increase in concentration of high viscosity hydroxypropylmethylcellulose (HPMC) resulted in reduction of the release rate. The drug release was observed to be dependent on the level of enteric coating and ethyl cellulose coating, being slower at increased coating. The release mechanism of PHH followed zero-order shifting to dissolution dependent by the increase of HPMC content. The formulation was stable without change in drug release rate. In vivo study in human volunteers confirmed the similarity between test and innovator formulations. In conclusion, HPMC-based matrix tablets, which were further coated using methacrylic acid copolymer, were found to be suitable for the formulation of single layer-controlled release PHH.
Environmental risk assessment of paroxetine
Paroxetine hydrochloride hemihydrate (the active ingredient in Paxil) is a pharmaceutical compound used for the treatment of depression, social anxiety disorder, obsessive compulsive disorder, panic disorder, and generalized anxiety disorder. Paroxetine (PA) is extensively metabolized in humans, with about 97% of the parent compound being excreted as metabolites through the urine and feces of patients. Therefore PA and metabolites have the potential to be discharged into wastewater treatment systems after therapeutic use. PA and its major human metabolite (PM) were investigated using studies designed to describe physical/chemical characteristics and determine their fate and effects in the aquatic environment. A significant portion of the PM entering a wastewater treatment plant would be expected to biodegrade given the higher activated sludge solids concentrations present in a typical wastewater treatment plant. The potential for direct photolysis of PM is also possible based on photolysis results for PA itself. These results provide strong support for expecting that PA and PM residuals will not persist in the aquatic environment after discharge from a wastewater treatment facility. This conclusion is also supported by the results of a USGS monitoring study, where no PM was detected in any of the samples at the 260 ng/L reporting limit. The results presented here also demonstrate the importance of understanding the human metabolism of a pharmaceutical so that the appropriate molecule(s) is used for fate and effects studies. In addition to the PA fate studies, PM was investigated using studies designed to determine potential environmental effects and a predicted no effect level (PNEC). The average measured activated sludge respiration inhibition value (EC50) for PM was 82 mg/L. The measured Microtox EC50 value was 33.0 mg/L, while the Daphnia magna EC50 value was 35.0 mg/L. The PNEC for PM was calculated to be 35.0 microg/L. Fate data were then used in a new watershed-based environmental risk assessment model, PhATE, to predict environmental concentrations (PECs). Comparison of the calculated PECs with the PNEC allows an assessment of potential environmental risk. Within the 1-99% of stream segments in the PhATE model, PEC values ranged from 0.003 to 100 ng/L. The risk assessment PEC/PNEC ratios ranged from approximately 3 x 10(-8) to approximately 3 x 10(-3), indicating a wide margin of safety, since a PEC/PNEC ratio <1 is generally considered to represent a low risk to the environment. In addition, Microtox studies carried out on PM biodegradation byproducts indicated no detectable residual toxicity. Any compounds in the environment as a result of the biodegradation of PM should be innocuous polar byproducts that should not exert any toxic effects.