Paroxetine  (Synonyms: BRL29060)

Paroxetine (BRL29060) is an orally active and selective serotonin reuptake inhibitor (SSRI) and apoptosis inducer with blood-brain barrier permeability. Paroxetine inhibits nitric oxide synthase and CYP2D6, induces desensitization of 5-HT1A/1B/1D autoreceptors, downregulates 5-HT2 receptors, and promotes the production of inflammatory cytokines. Paroxetine is a weak norepinephrine (NE) uptake inhibitor and possesses antitumor activity. Paroxetine is widely used in research concerning depression, obsessive-compulsive disorder, panic disorder, social phobia, generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, hot flashes, and related conditions^{[1][2][3][4][5][6]}.

Paroxetine potently and selectively inhibits serotonin reuptake in rat brain synaptosomes, with a K_i of 1.1 nmol/L, and shows much weaker activity against norepinephrine and dopamine reuptake^[1].
Paroxetine has no significant affinity for most tested neurotransmitter receptors in rat brain tissue, only showing weak binding to muscarinic cholinergic receptors with a K_i of 89 nmol/L^[1].
Paroxetine (76 nM) exhibits high affinity for the muscarinic M1 receptor, resulting in greater anticholinergic effects than other SSRIs^[2].
Paroxetine exhibits estrogenic activity in an in vitro assay that identifies chemicals disrupting aromatase and estrogen balance in humans, which may promote estrogen-sensitive breast tumor growth^[2].
Paroxetine (10-20 μM; 6-24 h) differentially modulates LPS-induced cytokine production in Raw264.7 mouse macrophages, potently inhibiting IL-6 production and enhancing TNFα production at 10 μM and 20 μM concentrations after 6 and 24 hours of incubation^[3].
Paroxetine (10-20 μM; 6-24 h) differentially modulates LPS-induced cytokine production in thioglycollate-elicited primary mouse peritoneal macrophages, potently inhibiting IL-6 production and enhancing TNFα production at 10 μM and 20 μM concentrations after 6 and 24 hours of incubation^[3].
Paroxetine (20 μM; 24 h) inhibits LPS-induced IL-6 production independent of 5-HT2/5-HT7 receptors and enhances LPS-induced TNFα production via 5-HT2/5-HT7 receptors in Raw264.7 mouse macrophages after 24 hours of incubation^[3].
Paroxetine (20 μM) modulates LPS-induced IL-6 and TNFα production in Raw264.7 mouse macrophages independently of GRK2, as its inhibitory effect on IL-6 and enhancing effect on TNFα are retained in GRK2-knockdown cells^[3].
Paroxetine (10-30 μM, 72 h) reduces the viability of MCF-7 cells in a time- and dose-dependent manner^[4].
Paroxetine (10-30 μM, 1-12 h) induces mitochondrial-mediated apoptosis in MCF-7, increasing ROS generation^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Paroxetine (8-32 mg/kg) produces a dose-dependent anti-immobility effect in the mouse forced swim test and also exhibits noradrenergic activity^[1].
Paroxetine exerts no significant dopaminergic, sedative, or ethanol-potentiating effects in healthy rodent models^[1].
Paroxetine produces extremely mild cardiovascular effects in healthy cats, rabbits, and dogs compared with tricyclic antidepressants, and exhibits weak quinidine-like activity only at serotonin reuptake-blocking doses^[1].
Combination of Paroxetine with monoamine oxidase inhibitors (MAOIs) or serotonin precursors induces serotonin syndrome in rats^[1].
Paroxetine modulates the hypothalamic-pituitary-adrenal axis and prolactin-related endocrine activity in healthy rats^[1].
Acute treatment with Paroxetine (5 mg/kg) increases extracellular serotonin levels in the brain of healthy rats^[1].
Paroxetine antagonizes apomorphine-induced hypothermia in rats, indicating that it exhibits noradrenergic activity at high doses^[1].
Combination treatment with Paroxetine (for 3 consecutive weeks) and Pravastatin (HY-B0165) increases the blood glucose level of prediabetic, insulin-resistant mice from 128 mg/dl to 193 mg/dl^[2].
Paroxetine (10 mg/kg, i.p., once a day for 14 days) reduces neurogenic pain in rats both before and after sciatic nerve injury^[5].
Paroxetine (0.3-10 mg/kg, orally, single dose) has anti-anxiety and antidepressant effects in rats, increasing social interaction time^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

329.37

C₁₉H₂₀FNO₃

61869-08-7

Liquid (Density: 1.213±0.06 g/cm³)

Colorless to light yellow

FC1=CC=C(C=C1)[C@H]2[C@@H](CNCC2)COC3=CC=C4OCOC4=C3

Room temperature in continental US; may vary elsewhere.

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Bourin M, et al. Paroxetine: a review[J]. CNS drug reviews, 2001, 7(1): 25-47.

  [2]. Nevels RM, et al. Paroxetine-The Antidepressant from Hell? Probably Not, But Caution Required. Psychopharmacology bulletin. 2016 Mar 01;46(1):77-104.  [Content Brief]

  [3]. Durairaj H, et al. Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages. International immunopharmacology. 2015 Apr;25(2):485-92.  [Content Brief]

  [4]. Young-Woo Cho, et al. Paroxetine Induces Apoptosis of Human Breast Cancer MCF-7 Cells through Ca2+-and p38 MAP Kinase-Dependent ROS Generation. Cancers (Basel). 2019 Jan 9;11(1):64.  [Content Brief]

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

  [6]. S Lightowler, et al. Anxiolytic-like effect of paroxetine in a rat social interaction test. Pharmacol Biochem Behav. 1994 Oct;49(2):281-5.  [Content Brief]