BLOCKADE BY NEWLY-DEVELOPED ANTIDEPRESSANTS OF BIOGENIC-AMINE UPTAKE INTO RAT-BRAIN SYNAPTOSOMES
BLOCKADE BY NEWLY-DEVELOPED ANTIDEPRESSANTS OF BIOGENIC-AMINE UPTAKE INTO RAT-BRAIN SYNAPTOSOMES
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DOI：
10.1016/0024-3205(93)90194-8
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发表时间：
1993-01-01
期刊：
影响因子：
6.1
通讯作者：
RICHELSON, E
中科院分区：
文献类型：
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作者：
BOLDENWATSON, C;RICHELSON, E
我们测定了8种新型抗抑郁药（依托哌酮、非莫西汀、洛非帕明、奈法唑酮、帕罗西汀、舍曲林、托莫西汀和文拉法辛）、2种新型抗抑郁药代谢产物（去甲基舍曲林和去甲氟西汀）、7种既往报道的抗抑郁药和卡马西平的摄取阻滞作用。从分别从海马、额叶皮质和纹状体制备的大鼠脑突触体中[H-3]去甲肾上腺素、[H-3]5-羟色胺和[H-3]多巴胺的竞争性摄取研究中获得摄取阻断的抑制剂常数（K（i）s）。在较新的化合物中，托莫西汀（K（i）= 0.7 nM）和洛非帕明（K（i）= 1.9 nM）是有效和选择性的[H-3]去甲肾上腺素摄取阻断剂;帕罗西汀（K（i）= 0.73 nM）、舍曲林（K（i）= 3.4 nM）和非莫西汀（K（i）= 22 nM）有效和选择性地抑制[H-3]5-羟色胺摄取。虽然没有一种药物对[H-3]多巴胺摄取阻断有效，但舍曲林是最有效的（K（i）= 260 nM）。这些数据有助于预测抗抑郁药的不良反应和药物相互作用。
We determined the uptake blockade produced by eight new antidepressant drugs (etoperidone, femoxetine, lofepramine, nefazodone, paroxetine, sertraline, tomoxetine, and venlafaxine), two metabolites of newer antidepressants (desmethylsertraline and norfluoxetine), seven previously reported antidepressants, and carbamazepine. Inhibitor constants (K(i)s) for uptake blockade were obtained from competitive uptake studies with [H-3]norepinephrine, [H-3]5-hydroxytryptamine, and [H-3]dopamine in rat brain synaptosomes prepared from hippocampus, frontal cortex, and striatum, respectively. Among the newer compounds, tomoxetine (K(i) = 0.7 nM) and lofepramine (K(i) = 1.9 nM) were potent and selective [H-3]norepinephrine uptake blockers; paroxetine (K(i) = 0.73 nM), sertraline (K(i) = 3.4 nM), and femoxetine (K(i) = 22 nM) potently and selectively inhibited [H-3]5-hydroxytryptamine uptake. Although none of the drugs was potent for [H-3]dopamine uptake blockade, sertraline was the most potent (K(i) = 260 nM). These data are useful in predicting adverse effects and drug-drug interactions of antidepressants.