Paroxetine HCl (BRL-29060A, FG-7051) is an antidepressant drug of the SSRI type.
Paroxetine apparently exerts their antidepressant activity by increasing the concentration of 5-HT in the extracellular compartment, thereby enhancing serotoninergic neurotransmission. Paroxetine (1-300 μM) results in a concentration-dependent reduction in the firing rate of DRN serotoninergic neurons with IC50 values of 1.4 μM in the ACSF superfusing brain stem slices. [1] Paroxetine is a highly potent inhibitor of desipramine hydroxylation, the inhibition constant (Ki) value of 2.0 mM indicated greater inhibiting potency than fluoxetine or norfluoxetine. [2] Paroxetine is shown to be a potent (Ki = 1.1 nM) and specific inhibitor of [3H]-5-hydroxytryptamine (5-HT) uptake into rat cortical and hypothalamic synaptosomes in vitro. Paroxetine demonstrates weak affinity for muscarinic receptors (Ki = 89 nM) but is at least 15 fold weaker than amitriptyline (Ki = 5.1 nM). [3] Paroxetine inactivates CYP2D6 via the formation of a metabolite intermediate complex. [4]
Paroxetine produces a dose-related inhibition of [3H]-5-HT uptake (ED50 = 1.9 mg/kg) into rat hypothalamic synaptosomes ex vivo with little effect on [3H]-l-noradrenaline (NA) uptake (ED50 greater than 30 mg/kg). Paroxetine (ED50 1-3 mg/kg PO) prevents the 5-HT depleting effect of p-chloroamphetamine (PCA) in rat brain, demonstrating 5-HT uptake blockade in vivo. [3]
[1] Le Poul E, et al. Naunyn Schmiedebergs Arch Pharmacol, 1995, 352(2), 141-148. [2] von Moltke LL, et al. J Clin Psychopharmacol, 1995, 15(2), 125-131. [3] Thomas DR, et al. Psychopharmacology (Berl), 1987, 93(2), 193-200.