Paroxetine binding to the rat
norepinephrine transporter in vivo

Owens MJ, Knight DL, Nemeroff CB
Department of Psychiatry and Behavioral Sciences,
Emory University School of Medicine,
Georgia 30322, USA.
Biol Psychiatry 2000 May 1; 47(9):842-5


BACKGROUND: The norepinephrine transporter (NET)/uptake site is an antidepressant-sensitive transporter located on plasma membranes of noradrenergic neurons and other specialized cells that remove norepinephrine (NE) from the synapse to terminate the actions of NE. The antidepressant paroxetine is believed to produce its therapeutic effects primarily by acting as a highly selective antagonist of the serotonin transporter (SERT). However, in vitro data indicates that paroxetine inhibits the NET. The present study was designed to determine whether paroxetine inhibits in NET in vivo. METHODS: Rats were administered paroxetine (6.5, 10.0, or 15.0 mg/kg/day) via osmotic minipumps for 1 week. Following attainment of steady state serum concentrations, cortical NET function was assessed by both [3H]-nisoxetine binding and [3H]-norepinephrine uptake assays conducted ex vivo. RESULTS: In unwashed brain homogenates, serum paroxetine concentrations greater than 100 ng/mL were positively correlated with the observed Kd for [3H]-nisoxetine. At [3H]-nisoxetine concentrations associated with 50% transporter occupancy in vehicle treated rats, [3H]-nisoxetine binding was decreased 21% and 34% in rats exhibiting serum paroxetine concentrations > 100 ng/mL and > 500 ng/mL, respectively. CONCLUSIONS: Although paroxetine is a very potent inhibitor of the SERT, paroxetine also inhibits the NET at serum concentrations > 100 ng/mL. This novel finding may underlie the broad therapeutic utility of paroxetine in mood and anxiety disorders.
Social phobia
Panic disorder
Paroxetine update
Paroxetine: review
Paroxetine: structure
Paroxetine and suicide
Paroxetine v bupropion
Paroxetine v fluoxetine
The serotonin syndrome
Paroxetine v citalopram
Paroxetine v maprotiline
SSRIs and panic disorder
Paroxetine v mirtazapine
Paroxetine for pathological gamblers
Venlafaxine versus paroxetine for OCD
Psychopharmacology of mood and anxiety disorders
Paroxetine (Paxil, Seroxat), pain and the opioid system

and further reading

Future Opioids
BLTC Research
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family