Details

Autor(en) / Beteiligte

• Bymaster, Frank P.
• Dreshfield-Ahmad, Laura J.
• Threlkeld, Penny G.
• Shaw, Janice L.
• Thompson, Linda
• Nelson, David L.
• Hemrick-Luecke, Susan K.
• Wong, David T.

Titel

Comparative Affinity of Duloxetine and Venlafaxine for Serotonin and Norepinephrine Transporters in vitro and in vivo, Human Serotonin Receptor Subtypes, and Other Neuronal Receptors

Ist Teil von

• Neuropsychopharmacology (New York, N.Y.), 2001-12, Vol.25 (6), p.871-880

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 Ki values of 7.5 and 0.8 nM, respectively, and with a Ki ratio of 9. Venlafaxine inhibited binding to the human NE and 5-HT transporters with Ki values of 2480 and 82 nM, respectively, and with a Ki ratio of 30. Duloxetine inhibited ex vivo binding to rat 5-HT transporters and NE transporters with ED50 values of 0.03 and 0.7 mg/kg, respectively, whereas venlafaxine had ED50 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 ED50 values of 2.3 and 12 mg/kg, respectively. Venlafaxine had ED50 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.