Ross S B, Renyi A L
Acta Pharmacol Toxicol (Copenh). 1975;36(Suppl 5):382-94. doi: 10.1111/j.1600-0773.1975.tb00806.x.
The simultaneous uptake of 3-H-l-noradrenaline (NA) and 14-C-5-hydroxytryptamine (5-HT) in slices from the midbrain-hypothalamus region of the rat brain was compared with the corresponding uptake in crude synaptosome preparations of the same brain region. In both preparations the uptake of the two amines was selective at the concentration used (1 times 10- minus 7 M or lower). The KM values for the amines (NA: 2 times 10- minus 7 M in synaptosomes and 5 times 10- minus 7 M in slices; 5-HT: 8 times 10- minus 8 M in synaptosomes and 6 times 10- minus 7 M in slices) and the inhibitory concentrations (IC50) of the antidepressant agents were lower in the synaptosome experiments than in the slices experiments. Moreover the order of the inhibitory activities differed between the two preparations. In the slices experiments the NA uptake was inhibited most markedly by desipramine followed by imipramine greater than chlorimipramine = nortriptyline greater than or equal to amitriptyline greater than or equal to chlordesipramine whereas in the synaptosome experiments the order was desipramine greater than nortriptyline greater than or equal to chlordesipramine greater than or equal to imipramine greater than amitriptyline greater than or equal to chlorimipramine. For the 5-HT uptake in slices the order of activity was: chlorimipramine greater than imipramine greater than or equal to amitriptyline greater than or equal to chlordesipramine = desipramine greater than or equal to nortriptyline whereas in the synaptosome preparations the order was: chlorimipramine greater than imipramine greater than or equal to amitriptyline greater than or equal to chlordesipramine greater than nortriptyline = desipramine. The role of protein binding and diffusion barriers in the causation of the difference in the results obtained with the two preparations is discussed.
将大鼠脑的中脑 - 下丘脑区域切片中3 - H - l - 去甲肾上腺素（NA）和14 - C - 5 - 羟色胺（5 - HT）的同时摄取情况，与同一脑区粗制突触体制剂中的相应摄取情况进行了比较。在这两种制剂中，在所使用的浓度（1×10⁻⁷M或更低）下，两种胺的摄取具有选择性。对于胺类物质（NA：突触体中为2×10⁻⁷M，切片中为5×10⁻⁷M；5 - HT：突触体中为8×10⁻⁸M，切片中为6×10⁻⁷M）的米氏常数（KM）以及抗抑郁药的抑制浓度（IC50），突触体实验中的数值低于切片实验中的数值。此外，两种制剂中抑制活性的顺序有所不同。在切片实验中，地昔帕明对NA摄取的抑制最为明显，其次是丙咪嗪，大于氯米帕明 = 去甲替林≥阿米替林≥氯氮卓，而在突触体实验中，顺序为地昔帕明＞去甲替林≥氯氮卓≥丙咪嗪≥阿米替林≥氯米帕明。对于切片中5 - HT的摄取，活性顺序为：氯米帕明＞丙咪嗪≥阿米替林≥氯氮卓 = 地昔帕明≥去甲替林，而在突触体制剂中，顺序为：氯米帕明＞丙咪嗪≥阿米替林≥氯氮卓＞去甲替林 = 地昔帕明。本文讨论了蛋白质结合和扩散屏障在导致两种制剂所得结果差异中的作用。
