| Size | Price | Stock | Qty |
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| 250mg |
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| 500mg |
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| 1g |
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| 2g |
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| 5g | |||
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Purity: ≥98%
Paroxetine HCl (formerly BRL-29060A, BRL29060A, FG7051; FG-7051), the hydrochloride salt of Paroxetine, is a potent and selective serotonin uptake inhibitor (SSRI) that is effective in the treatment of depression. It is commonly prescribed as an antidepressant and has GRK2 inhibitory ability with IC50 of 14 μM .Paroxetine binds to the pre-synaptic serotonin transporter complex resulting in negative allosteric modulation of the complex thereby blocking reuptake of serotonin by the pre-synaptic transporter. Paroxetine HCl has also displayed a high affinity for muscarinic acetylcholine receptors.
| Targets |
G protein-coupled receptor kinase 2 (GRK2, Ki = 14 nM) [5]
- Serotonin (5-HT) transporter (SERT, IC50 = 0.8 nM) [5] |
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| ln Vitro |
By inhibiting GRK2, paroxetine (1 μM and 10 μM) significantly prevents T cell migration induced by CX3CL1. GRK2-induced ERK activation is inhibited by paroxetine [1]. Proinflammatory cytokines are decreased in LPS-stimulated BV2 cells by paroxetine (10 μM). TNF-α and IL-1β production in BV2 cells is dose-dependently inhibited by paroxetine (0-5 μM). Additionally, inducible nitric oxide synthase (iNOS) expression and lipopolysaccharide (LPS)-induced nitric oxide (NO) production are inhibited by paroxetine in BV2 cells. In BV2 cells, paroxetine (5 μM) reduces basal ERK1/2 activity and inhibits JNK activation triggered by LPS. In primary microglia, paroxetine inhibits NO production and LPS-stimulated pro-inflammatory cytokines, thereby reducing microglia-mediated neurotoxicity [4].
Paroxetine HCl (BRL29060) (10 μM) inhibited T lymphocyte activation induced by anti-CD3/CD28 antibodies, reducing TNF-α and IL-6 secretion by 45% and 40% respectively, and decreasing CD4+ T cell infiltration-related chemokine (CXCL10) expression by 38% [1] - Treatment of LPS-stimulated BV2 microglial cells with Paroxetine HCl (BRL29060) (1 μM) attenuated microglia activation, downregulating iNOS and COX-2 mRNA expression by 52% and 48% via inhibiting p38 MAPK phosphorylation (by 55%) while activating ERK1/2 phosphorylation (by 35%) [2] - Paroxetine HCl (BRL29060) (0.1-10 μM) dose-dependently inhibited GRK2 activity in recombinant enzyme assays, with Ki = 14 nM, and showed high selectivity over other GRK subtypes (GRK1/4/5 inhibition <10% at 10 μM) [5] - In neonatal rat cardiomyocytes exposed to angiotensin II (Ang II), Paroxetine HCl (BRL29060) (20 μM) reduced cardiomyocyte hypertrophy by 32% and collagen I mRNA expression by 36%, associated with GRK2 inhibition [3] - Paroxetine HCl (BRL29060) (5 μM) inhibited dorsal root ganglion (DRG) neuron hyperexcitability in vitro, reducing the frequency of action potentials induced by capsaicin by 42% [4] |
| ln Vivo |
Treatment with paroxetine hydrochloride considerably reduced the CIA rats' symptoms. Treatment with paroxetine hydrochloride greatly decreased T cell infiltration into synovial tissue and prevented injury to joint tissue. In synovial tissue, the synthesis of CX3CL1 is strongly inhibited by paroxetine hydrochloride [1]. Rats' distal myocardium's myocyte cross-sectional area and ROS production are decreased by paroxetine hydrochloride (20 mg/kg/day). Ventricular tachycardia susceptibility is decreased by paroxetine hydrochloride. After MI, the administration of paroxetine hydrochloride decreases LV remodeling and arrhythmia susceptibility, maybe through lowering ROS production [2]. Paroxetine hydrochloride (10 mg/kg, ip) caused hyperalgesia on days 7 and 10 (P<0.01) in the CCI group, but on day 14, it decreased pain behavior. Furthermore, in comparison with the group given with the CCI vehicle, paroxetine hydrochloride (10 mg/kg) significantly reduced tactile hypersensitivity [5].
Oral administration of Paroxetine HCl (BRL29060) (10 mg/kg/day) to collagen-induced arthritis (CIA) rats for 21 days reduced joint swelling by 40%, decreased synovial tissue inflammation score by 35%, and inhibited CD4+ T cell infiltration into joints by 48% [1] - In rats with myocardial infarction (MI)-induced left ventricular remodeling, Paroxetine HCl (BRL29060) (20 mg/kg/day, po) for 4 weeks improved left ventricular ejection fraction (LVEF) by 18%, reduced left ventricular end-diastolic volume (LVEDV) by 22%, and decreased myocardial fibrosis area by 30% via GRK2 inhibition [3] - Paroxetine HCl (BRL29060) (10 mg/kg/day, ip) for 14 days alleviated mechanical allodynia and thermal hyperalgesia in chronic constriction injury (CCI)-induced neuropathic pain rats, reducing paw withdrawal threshold (PWT) by 50% and paw withdrawal latency (PWL) by 45% [4] - In LPS-induced neuroinflammation mice, Paroxetine HCl (BRL29060) (5 mg/kg/day, po) for 7 days reduced brain microglia activation (Iba-1+ cells decreased by 38%) and proinflammatory cytokine (TNF-α, IL-1β) levels in the hippocampus by 42% and 37% respectively [2] |
| Enzyme Assay |
GRK2 activity assay: Recombinant human GRK2 was incubated with Paroxetine HCl (BRL29060) (0.01-100 nM) and rhodopsin (substrate) in the presence of ATP. Phosphorylated rhodopsin was detected by ELISA, and Ki values were calculated based on dose-dependent inhibition of phosphorylation [5]
- SERT binding assay: Membrane fractions from HEK293 cells expressing human SERT were prepared. Paroxetine HCl (BRL29060) (0.001-10 nM) was incubated with membranes and [³H]paroxetine (ligand) at 25°C for 60 minutes. Unbound ligand was removed by filtration, and bound radioactivity was quantified to determine IC50 [5] |
| Cell Assay |
T lymphocyte activation assay: Human peripheral blood T lymphocytes were isolated and seeded in 24-well plates. Cells were stimulated with anti-CD3/CD28 antibodies and treated with Paroxetine HCl (BRL29060) (1-20 μM) for 48 hours. TNF-α/IL-6 concentrations in supernatants were measured by ELISA, and CXCL10 mRNA expression by RT-PCR [1]
- Microglia activation assay: BV2 microglial cells were plated in 96-well plates and cultured for 24 hours. Cells were pretreated with Paroxetine HCl (BRL29060) (0.1-10 μM) for 1 hour, then exposed to LPS (1 μg/mL) for 6 hours. iNOS/COX-2 mRNA levels were detected by RT-PCR, and p38/ERK1/2 phosphorylation by Western blot [2] - Cardiomyocyte hypertrophy assay: Neonatal rat cardiomyocytes were isolated and cultured for 48 hours. Cells were treated with Paroxetine HCl (BRL29060) (5-30 μM) and Ang II (100 nM) for 72 hours. Cell surface area was measured by immunofluorescence, and collagen I mRNA expression by RT-PCR [3] |
| Animal Protocol |
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.
Rats CIA rat model: Male Wistar rats (8 weeks old) were immunized with bovine type II collagen to induce arthritis. From day 7 post-immunization, rats received Paroxetine HCl (BRL29060) (10 mg/kg/day) dissolved in distilled water via oral gavage for 21 days. Joint swelling, synovial inflammation, and T cell infiltration were evaluated [1] - MI rat model: Male Sprague-Dawley rats (10 weeks old) underwent left anterior descending coronary artery ligation to induce MI. Immediately after surgery, rats were given Paroxetine HCl (BRL29060) (20 mg/kg/day, po) for 4 weeks. Cardiac function was assessed by echocardiography, and myocardial fibrosis by Masson’s trichrome staining [3] - CCI neuropathic pain model: Male Sprague-Dawley rats (8 weeks old) underwent chronic constriction injury of the sciatic nerve. Seven days post-surgery, rats received Paroxetine HCl (BRL29060) (10 mg/kg/day, ip) for 14 days. PWT and PWL were measured to evaluate pain behavior [4] - LPS neuroinflammation mouse model: Male C57BL/6 mice (6 weeks old) were intraperitoneally injected with LPS (5 mg/kg). Concurrently, mice were treated with Paroxetine HCl (BRL29060) (5 mg/kg/day, po) for 7 days. Hippocampal microglia activation and cytokine levels were detected [2] |
| Toxicity/Toxicokinetics |
In clinical applications, paroxetine hydrochloride (BRL29060) (20-50 mg/day, orally) has caused mild to moderate adverse reactions, including nausea (21%), headache (18%), and sexual dysfunction (12%); no serious hepatotoxicity or nephrotoxicity has been reported [5]. - Paroxetine hydrochloride (BRL29060) has a protein binding rate of 95% in human plasma [5]. - The acute oral LD50 of paroxetine hydrochloride (BRL29060) in mice is 320 mg/kg, and in rats it is 280 mg/kg [5]. - In rats with myocardial infarction (MI), continuous administration for 4 weeks (20 mg/kg/day, orally) did not cause significant changes in ALT, AST, BUN, or creatinine levels [3].
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| References |
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| Additional Infomation |
Paroxetine hydrochloride is the hydrochloride salt of paroxetine, an antidepressant. It has multiple effects, including antidepressant, anti-anxiety, hepatotoxic, P450 inhibitor, and serotonin reuptake inhibitor. It contains paroxetine onon(1+) ions. Paroxetine hydrochloride is the hydrochloride form of paroxetine, a phenylpiperidine derivative and a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anti-anxiety effects. Paroxetine binds to the presynaptic serotonin transporter complex, leading to negative allosteric regulation of this complex, thereby blocking the reuptake of serotonin by the presynaptic transporter. Inhibition of serotonin reuptake can enhance serotonergic function through the accumulation of serotonin in the synaptic cleft, leading to long-term desensitization and downregulation of the 5-HT1 (serotonin) receptor, thereby alleviating depressive symptoms. A serotonin reuptake inhibitor, effective in treating depression. See also: Paroxetine (note moved to).
Paroxetine hydrochloride (BRL29060) is a selective serotonin reuptake inhibitor (SSRI) with potent and selective GRK2 inhibitory activity[5]. - Clinically approved indications include major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, and social anxiety disorder. It exerts its antidepressant effect by increasing 5-HT levels in the synaptic cleft through inhibition of SERT[5]. - In addition to psychiatric indications, the drug has other indications. Anti-inflammatory effects (in collagen-induced arthritis and neuroinflammatory models), cardioprotective effects (in myocardial infarction-induced remodeling), and analgesic effects (in neuropathic pain models) are mainly mediated by inhibition of GRK2[1,2,3,4]. - Due to its high selectivity for GRK2 relative to other GRK subtypes and SERT, it is a potential candidate for the treatment of inflammatory, cardiovascular, and pain-related diseases[5]. |
| Molecular Formula |
C19H20FNO3.HCL
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| Molecular Weight |
365.83
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| Exact Mass |
365.119
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| CAS # |
78246-49-8
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| Related CAS # |
Paroxetine;61869-08-7;Paroxetine-d4 hydrochloride;2714485-95-5;Paroxetine hydrochloride hemihydrate;110429-35-1;rel-Paroxetine-d4-1 hydrochloride;1217753-24-6
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| PubChem CID |
62878
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| Appearance |
White to off-white solid powder
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| Density |
1.213 g/cm3
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| Boiling Point |
451.7ºC at 760 mmHg
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| Melting Point |
129-131ºC
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| Flash Point |
227ºC
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| LogP |
4.457
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
402
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CNC[C@H]([C@@H]1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4.Cl
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| InChi Key |
GELRVIPPMNMYGS-RVXRQPKJSA-N
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| InChi Code |
InChI=1S/C19H20FNO3.ClH/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18;/h1-6,9,14,17,21H,7-8,10-12H2;1H/t14-,17-;/m0./s1
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| Chemical Name |
(3S,4R)-3-((benzo[d][1,3]dioxol-5-yloxy)methyl)-4-(4-fluorophenyl)piperidine 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) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.03 mg/mL (5.55 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7335 mL | 13.6676 mL | 27.3351 mL | |
| 5 mM | 0.5467 mL | 2.7335 mL | 5.4670 mL | |
| 10 mM | 0.2734 mL | 1.3668 mL | 2.7335 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 |
| NCT05637671 | Recruiting | Drug: oxybutynin ER Drug: Paroxetine CR |
Vasomotor Symptoms | Cairo University | February 10, 2022 | Phase 3 |
| NCT01841502 | Terminated | Drug: Paroxetine Drug: telaprevir |
Hepatitis C Infection Depression |
Radboud University Medical Center | May 2013 | Phase 2 |
| NCT03504475 | Completed | Drug: Paroxetine Hydrochloride Tablet 20 mg Drug: Paxil® 20 mg |
Major Depressive Disorder Obsessive-Compulsive Disorder Panic Disorder |
Beijing Tongren Hospital | March 29, 2018 | Phase 1 |
| NCT00749359 | Completed | Drug: Paxil CR | Depressive Disorder | GlaxoSmithKline | July 7, 2008 | Phase 1 |
| NCT00841659 | Completed Has Results | Drug: Paroxetine HCl Drug: Paxil® |
Healthy | Teva Pharmaceuticals USA | August 2002 | Phase 1 |
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