Paroxetine

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]}. In Vitro: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]. In Vivo: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].