Duloxetine (LY 248686): an inhibitor of serotonin and noradrenaline uptake and an antidepressant drug candidate
- 1 October 1998
- journal article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 7 (10) , 1691-1699
- https://doi.org/10.1517/13543784.7.10.1691
Abstract
Duloxetine is a potent inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NE) uptake in vitro and in vivo and is 3- to 5-times more effective at inhibiting 5-HT uptake. Duloxetine is a weak inhibitor of dopamine (DA) uptake and the binding of radioligands to neurotransmitter receptors. Upon administration of duloxetine in vivo, the inhibitory effects on uptake of 5-HT and NE persist for up to 8 h. Desmethylduloxetine, a potential metabolite, is also an inhibitor of 5-HT and NE uptake. Consistent with the ability to inhibit the uptake of 5-HT, duloxetine blocks p-chloroamphetamine induced depletion of mouse and rat brain 5-HT. Duloxetine also blocks the 6-hydroxydopamine induced depletion of mouse heart NE and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced depletion of NE in frontal cortex but does not block the MPTP induced depletion of DA in rat striatum. Electrophysiological studies show that duloxetine decreases the activity of 5-HT neurones in dorsal raphe and at a 5-ti...Keywords
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