Hyttel J
Psychopharmacology (Berl). 1978 Dec 15;60(1):13-8. doi: 10.1007/BF00429172.
The uptake of 3H-5-HT in synaptosomes from rat brains was investigated. Addition of DA or NA had only a slight or no effect on the uptake. When the uptake into NA and DA neurons was inhibited by the addition of high concentrations of NA and DA, the uptake of 3H-5-HT was unchanged. This was also found after destruction of NA and DA neurons by 6-hydroxydopamine treatment. Furthermore, the uptake of 3H-5-HT was almost equal in different brain parts containing NA and DA in very different amounts. These observations show that the uptake measured with 3H-5-HT is specific for 5-HT neurons. The present study revealed that citalopram and chlorimipramine inhibited uptake competitively, and in this respect the two drugs were equipotent. Compared with a series of tricyclic thymoleptics, the two drugs were the most potent inhibitors of 5-HT uptake, about 20 to 35 times more active than imipramine and amitriptyline. The metabolites of citalopram were also rather potent. The results obtained in the present study correlate closely with those obtained using inhibition of 14C-5-HT uptake in blood platelets, or using the inhibition of H 75/12-induced 5-HT depletion in rat brain. When rats were treated orally with citalopram or chlorimipramine, the inhibition of 3H-5-HT uptake in synaptosomes derived from these rats was two times greater after citalopram than after chlorimipramine.
研究了大鼠脑突触体中3H-5-羟色胺（3H-5-HT）的摄取情况。添加多巴胺（DA）或去甲肾上腺素（NA）对摄取仅有轻微影响或无影响。当通过添加高浓度的NA和DA抑制NA和DA神经元的摄取时，3H-5-HT的摄取未发生变化。在用6-羟基多巴胺处理破坏NA和DA神经元后也得到了同样的结果。此外，在含有不同量NA和DA的不同脑区中，3H-5-HT的摄取几乎相等。这些观察结果表明，用3H-5-HT测量的摄取对5-HT神经元具有特异性。本研究表明，西酞普兰和氯米帕明竞争性抑制摄取，在这方面两种药物效力相当。与一系列三环类抗抑郁药相比，这两种药物是最有效的5-HT摄取抑制剂，活性比丙咪嗪和阿米替林高约20至35倍。西酞普兰的代谢产物也相当有效。本研究获得的结果与使用抑制血小板中14C-5-HT摄取或使用抑制大鼠脑中H 75/12诱导的5-HT耗竭所获得的结果密切相关。当给大鼠口服西酞普兰或氯米帕明时，来自这些大鼠的突触体中3H-5-HT摄取的抑制在西酞普兰处理后比氯米帕明处理后大两倍。
