Paroxetine HCl

Paroxetine hydrochloride is a potent selective serotonin-reuptake inhibitor, commonly prescribed as an antidepressant and has GRK2 inhibitory ability with IC50 of 14 μM.

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Neuronal Signaling >> Serotonin Transporter

Research Areas >> Neurological Disease

IC50: 14 μM (GRK2)[3]

Paroxetine (1 μM and 10 μM) distinctly restrains T cell migration induced by CX3CL1 through inhibiting GRK2. Paroxetine inhibits GRK2 induced activation of ERK[1]. Paroxetine (10 μM) reduces pro-inflammatory cytokines in LPS-stimulated BV2 cells. Paroxetine (0-5 μM) leads to a dose-dependent inhibition on LPS-induced production of TNF-α and IL-1β in BV2 cells. Paroxetine also inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in BV2 cells. Paroxetine (5 μM) blocks LPS-induced JNK activation and attenuates baseline ERK1/2 activity in BV2 cells. Paroxetine relieves microglia-mediated neurotoxicity, and suppresses LPS-stimulated pro-inflammatory cytokines and NO in primary microglial cells[4].

Paroxetine treatment obviously attenuates the symptoms of CIA rats. Paroxetine treatment clearly prevents the histological damage of joints and alleviates T cells infiltration into synovial tissue. Paroxetine reveals a strong effect on inhibiting CX3CL1 production in synovial tissues[1]. Paroxetine (20 mg/kg/day) reduces the myocyte cross-sectional area in rat and ROS formation in the remote myocardium. Paroxetine reduces the susceptibility to ventricular tachycardia. Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation[2]. In CCI paroxetine-treated group, paroxetine (10 mg/kg, i.p.) produces hyperalgesia at days 7 and 10 (P<0.01), but a decrease in pain behavior is seen at day 14. Moreover, paroxetine (10 mg/kg) significantly attenuates tactile hypersensitivity when compared to CCI vehicle-treated group[5].

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.

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.

[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.

[2]. Lassen TR, et al. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction. Basic Res Cardiol. 2017 May;112(3):26.

[3]. Waldschmidt HV, et al. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069.

[4]. Liu RP, et al. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation. 2014 Mar 12;11:47.

[5]. Zarei M, et al. Paroxetine attenuates the development and existing pain in a rat model of neurophatic pain. Iran Biomed J. 2014;18(2):94-100.

Fluoxetine Hydrochloride | Sertraline hydrochloride | Fluvoxamine maleat | Duloxetine hydrochloride | Imipramine hydrochloride | Clomipramine HCl | Venlafaxine hydrochloride | Desvenlafaxine succinate | Doxepin hydrochloride | Vortioxetine | Milnacipran ((1S-cis) hydrochloride) | Vilazodone Hydrochloride | Dasotraline (hydrochloride) | Amitifadine (hydrochloride) | Cinchonidine

MOLECULAR FORMULA :

C19-H20-F-N-O3.Cl-H

MOLECULAR WEIGHT :

365.86

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

415 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ASSUA6 Acta Psychiatrica Scandinavica, Supplementum. (Munksgaard International Publishers, POB 2148, DK-1016 Copenhagen K, Denmark) No.160- 1961- Volume(issue)/page/year: 350,31,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

30 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ASSUA6 Acta Psychiatrica Scandinavica, Supplementum. (Munksgaard International Publishers, POB 2148, DK-1016 Copenhagen K, Denmark) No.160- 1961- Volume(issue)/page/year: 350,31,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

378 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ASSUA6 Acta Psychiatrica Scandinavica, Supplementum. (Munksgaard International Publishers, POB 2148, DK-1016 Copenhagen K, Denmark) No.160- 1961- Volume(issue)/page/year: 350,31,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

42 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ASSUA6 Acta Psychiatrica Scandinavica, Supplementum. (Munksgaard International Publishers, POB 2148, DK-1016 Copenhagen K, Denmark) No.160- 1961- Volume(issue)/page/year: 350,31,1989