Paroxetine hydrochloride (Paroxetine HCl) is a serotonin uptake inhibitor that is effective in the treatment of depression.

GRK2:14 μM

Paroxetine, at an ED50 of 1-3 mg/kg when administered orally (PO), demonstrates the capability to prevent the depletion of serotonin (5-HT) in rats' brains induced by p-chloroamphetamine (PCA), signifying an inhibition of serotonin uptake in vivo. Additionally, in isolated rat hypothalamic synaptosomes, paroxetine exhibits a dose-dependent inhibition of [3H] - 5-HT uptake with an ED50 of 1.9 mg/kg, while showing minimal effects on the uptake of [3H] - norepinephrine (NA), with an ED50 exceeding 30 mg/kg.

Paroxetine, a highly effective hydroxylated metabolite inhibitor of (dextromethorphan), demonstrates the concentration-dependent reduction in the firing rate of serotonergic neurons within the DRN of super fused brainstem slices at 1-300 μM, with an IC50 value of 1.4 μM. With an inhibition constant (Ki) of 2 mM, Paroxetine's inhibitory capacity surpasses that of fluoxetine or norfluoxetine, indicating its more potent effect. Moreover, in rat cortical and in vitro hypothalamic synapses, Paroxetine acts as a potent and specific inhibitor of [3H]-5-hydroxytryptamine (5-HT), with a Ki of 1.1 nM. Its antidepressant activity is attributed to the increased concentration of 5-HT in the extracellular compartment, thereby enhancing serotonergic neurotransmission. Paroxetine also inactivates CYP2D6 by forming metabolic intermediate complexes.

Paroxetine is dissolved in DMSO. 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.