Ki: 4 nM (NET), 61 nM (SERT), 78720 nM (DAT)

Treatment of rats with Desipramine hydrochloride for 14 days reduces norepinephrine transporter (NET) expression in a dose-dependent manner, as indicated by a reduction of the specific binding of ³ H-nisoxetine to the NET in preparations of cerebral cortex (F _(3,16) =4.33, p<0.05) and hippocampus (F _(3,16) =4.34, p<0.05). This NET down regulation is observed 2 days after discontinuation of chronic Desipramine hydrochloride treatment, a time when plasma and brain concentrations of Desipramine hydrochloride and desmethyldesipramine are undetectable (ie below the 25 ng detection limit of the assay).