Pharmacological profile of antidepressants and related compounds at human monoamine transporters
Pharmacological profile of antidepressants and related compounds at human monoamine transporters
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DOI：
10.1016/s0014-2999(97)01393-9
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发表时间：
1997-12-11
影响因子：
5
通讯作者：
Richelson, E
中科院分区：
文献类型：
--
作者：
Tatsumi, M;Groshan, K;Richelson, E
使用放射性配体结合分析，我们确定了平衡解离常数（K-D）的37种抗抑郁药，其代谢产物（去甲基西酞普兰，去甲基舍曲林，和norfluoxetine），一些情绪稳定剂，和各种其他化合物（一些抗癫痫药，钙离子通道拮抗剂，苯二氮卓类，精神兴奋剂，抗组胺药，和单胺类）的人血清素，去甲肾上腺素，多巴胺转运蛋白。在我们测试的化合物中，马吲哚对人去甲肾上腺素和多巴胺转运蛋白的作用最强，K-D分别为0.45 +/- 0.03 nM和8.1 +/- 0.4 nM。舍曲林（KD = 25 +/- 2 nM）和诺米芬辛（56 +/- 3 nM）是人类多巴胺转运蛋白中最有效的两种抗抑郁药。我们发现抗抑郁剂的亲和力在结合到5-羟色胺（R = 0.93），去甲肾上腺素（R = 0.97），多巴胺（R = 0.87）转运蛋白的显着相关性相比，其各自的值抑制摄取单胺进入大鼠脑突触体。这些数据有助于预测抗抑郁药和相关化合物的一些可能的不良反应和药物相互作用。(C)1997年Elsevier Science B.V.
Using radioligand binding assays, we determined the equilibrium dissociation constants (K-D's) for 37 antidepressants, three of their metabolites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol was the most potent at the human norepinephrine and dopamine transporters with K-D's of 0.45 +/- 0.03 nM and 8.1 +/- 0.4 nM, respectively. Sertraline (K-D = 25 +/- 2 nM) and nomifensine (56 +/- 3 nM) were the two most potent antidepressants at the human dopamine transporter. We showed significant correlations for antidepressant affinities at binding to serotonin (R = 0.93), norepinephrine (R = 0.97), and dopamine (R = 0.87) transporters in comparison to their respective values for inhibiting uptake of monoamines into rat brain synaptosomes. These data are useful in predicting some possible adverse effects and drug-drug interactions of antidepressants and related compounds. (C) 1997 Elsevier Science B.V.