Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors
by
Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL,
Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT.
Neuroscience Research Division,
Lilly Research Laboratories,
Lilly Corporate Center,
Indianapolis, IN 46285-0510, USA.
fbymaster@lilly.com
Neuropsychopharmacology 2001 Dec;25(6):871-80


ABSTRACT

The blockade of serotonin (5-HT) and norepinephrine (NE) transporters in vitro and in vivo by the dual 5-HT/NE reuptake inhibitors duloxetine and venlafaxine was compared. Duloxetine inhibited binding to the human NE and 5-HT transporters with K(i) values of 7.5 and 0.8 nM, respectively, and with a K(i) ratio of 9. Venlafaxine inhibited binding to the human NE and 5-HT transporters with K(i) values of 2480 and 82 nM, respectively, and with a K(i) ratio of 30. Duloxetine inhibited ex vivo binding to rat 5-HT transporters and NE transporters with ED(50) values of 0.03 and 0.7 mg/kg, respectively, whereas venlafaxine had ED(50) values of 2 and 54 mg/kg, respectively. The depletion of rat brain 5-HT by p-chloramphetamine and depletion of rat hypothalamic NE by 6-hydroxydopamine was blocked by duloxetine with ED(50) values of 2.3 and 12 mg/kg, respectively. Venlafaxine had ED(50) values of 5.9 and 94 mg/kg for blocking p-chloramphetamine- and 6-hydroxydopamine-induced monoamine depletion, respectively. Thus, duloxetine more potently blocks 5-HT and NE transporters in vitro and in vivo than venlafaxine.
SSRIs
NARIs
SNRIs
5-HT1a
Serotonin
Duloxetine
Milnacipran
Venlafaxine
Noradrenaline
Alpha2 antagonism
Duloxetine: hope or hype?
Duloxetine and depression
Duloxetine for fibromyalgia
Duloxetine (Cymbalta): structure
Duloxetine and urinary incontinence
Duloxetine for pain-ridden depressives
Physical symptoms comorbid with depression
Dual-action antidepressants and slimming-drugs
Duloxetine, a balanced serotonin-noradrenaline reuptake inhibitor
Duloxetine (Cymbalta) for depressives with and without melancholia


Refs
and further reading

HOME
HedWeb
Nootropics
erythroxylum-coca.com
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
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