Ishigooka J, Kasahara T, Nagata E, Murasaki M, Miura S
Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 1998 Feb;18(1):19-21.
The effect of a washing procedure on serotonin (5-HT) uptake in vitro was investigated using human platelets pretreated with nine 5-HT uptake inhibitors and various Ki values to confirm the assumption that a drug with high affinity for the 5-HT uptake site would be hardly removed and have a long-lasting effect in vivo. Among the drugs tested, those with low Ki values, such as clomipramine, duloxetine and paroxetine, inhibited 5-HT uptake even after removal from the medium, while those with high Ki values such as amitriptyline, desipramine, imipramine, mianserin, trazodone, and zimelidine were easily removed by washing. The results indicated that low Ki values might be proportionally related to the long-lasting binding of drugs to the 5-HT uptake site. The results also suggested that the threshold Ki value which could separate 5-HT uptake inhibitors with a probable long-lasting effect in vivo from those without the effect would be between 5 nM and 42 nM.
使用经九种5-羟色胺（5-HT）摄取抑制剂预处理且具有不同Ki值的人血小板，研究了洗涤程序对体外5-HT摄取的影响，以证实以下假设：对5-HT摄取位点具有高亲和力的药物在体内难以被清除且具有持久作用。在所测试的药物中，那些Ki值较低的药物，如氯米帕明、度洛西汀和帕罗西汀，即使从培养基中去除后仍能抑制5-HT摄取，而那些Ki值较高的药物，如阿米替林、去甲丙咪嗪、丙咪嗪、米安色林、曲唑酮和齐美利定，通过洗涤很容易被清除。结果表明，低Ki值可能与药物与5-HT摄取位点的持久结合成比例相关。结果还表明，能够将可能在体内具有持久作用的5-HT摄取抑制剂与无此作用的抑制剂区分开的阈值Ki值在5 nM至42 nM之间。
