rel-Paroxetine-d4 ( HCl) is an isotopically labeled Paroxetine HCl . Paroxetine HCl is an orally bioavailable serotonin-reuptake inhibitor that can suppress GRK2 with IC50 of 14 μM. Paroxetine HCl may be used in depression research.

Physicochemical Properties

Molecular Formula	C19H21CLFNO3
Molecular Weight	369.850994825363
Exact Mass	369.144
CAS #	1217683-35-6
PubChem CID	76973866
Appearance	Typically exists as solid at room temperature
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	25
Complexity	402
Defined Atom Stereocenter Count	2
SMILES	N1CC[C@@H](C2=C([2H])C([2H])=C(F)C([2H])=C2[2H])[C@H](COC2=CC=C3OCOC3=C2)C1.[H]Cl
InChi Key	GELRVIPPMNMYGS-TYPQLLAASA-N
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/i1D,2D,3D,4D;
Chemical Name	(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(2,3,5,6-tetradeuterio-4-fluorophenyl)piperidine;hydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 14 μM (GRK2)[2]; Serotonin-reuptake[4]
ln Vitro	Paroxetine (1 μM and 10 μM; 4 h) inhibits GRK2, which in turn distinctly inhibits T cell migration stimulated by CX3CL1[2]. Paroxetine (16 h) prevents splenic T cells' GRK2-induced ERK activation[2]. In BV2 cells treated with LPS, paroxetine (10 μM) decreases pro-inflammatory cytokines[3]. In BV2 cells, paroxetine (0-5 μM) inhibits the generation of TNF-α and IL-1β produced by LPS in a dose-dependent manner[3]. additionally prevents the generation of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) in BV2 cells when lipopolysaccharide (LPS) is present[3]. In BV2, paroxetine (5 μM) reduces baseline ERK1/2 activity and inhibits LPS-induced JNK activation. It also alleviates microglia-mediated neurotoxicity and inhibits LPS-stimulated pro-inflammatory cytokines and NO in primary microglial cells[3].
ln Vivo	In rats with collagen-induced arthritis (CIA), paroxetine (15 mg/kg/d; po; 15 d) clearly reduces the symptoms[2].
Animal Protocol	Animal/Disease Models: Collagen-induced arthritis (CIA) model in rats (around 14-day-old)[2] Doses: 15 mg/kg Route of Administration: po (oral gavage); one time/day; 15 days Experimental Results: Helped CIA rats to restore more body weight.
References	[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-223. [2]. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364. [3]. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation. 2014 Mar 12;11:47. [4]. Inhibitory effect of the selective serotonin reuptake inhibitor paroxetine on human Kv1.3 channels. Eur J Pharmacol. 2021 Dec 5;912:174567.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7038 mL	13.5190 mL	27.0380 mL
	5 mM	0.5408 mL	2.7038 mL	5.4076 mL
	10 mM	0.2704 mL	1.3519 mL	2.7038 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.