Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors
Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors
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DOI：
10.1016/s0893-133x(01)00298-6
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发表时间：
2001-12-01
影响因子：
7.6
通讯作者：
Wong, DT
中科院分区：
文献类型：
--
作者：
Bymaster, FP;Dreshfield-Ahmad, LJ;Wong, DT
比较了5-HT/去甲肾上腺素（NE）双重再摄取抑制剂度洛西汀和文拉法辛对5-HT和NE转运体的阻断作用。度洛沙汀抑制与人NE和5-HT转运蛋白的结合，Ki值分别为7.5和0.8 nM，Ki比为9。文拉法辛抑制与人NE和5-HT转运蛋白的结合，Ki值分别为2480和82 nM，Ki比为30。度洛沙汀抑制离体与大鼠5-HT转运体和NE转运体的结合，ED 50值分别为0.03和0.7 mg/kg，而文拉法辛的ED 50值分别为2和54 mg/kg。对氯苯丙胺对大鼠脑内5-HT的消耗和6-羟基多巴胺对大鼠下丘脑NE的消耗可被度洛沙汀阻断，ED_（50）值分别为2.3和12 mg/kg。文拉法辛阻断对氯苯丙胺和6-羟基多巴胺诱导的单胺耗竭的ED 50值分别为5.9和94 mg/kg。因此，度洛沙汀在体外和体内比文拉法辛更有效地阻断5-HT和NE转运蛋白。[Neuropsychopharmacology 25：871-880，2001]（C）2001年美国神经精神药理学学会。出版社：Elsevier Science Inc.
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 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. [Neuropsychopharmacology 25:871-880, 2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.