Riant P, Urien S, Albengres E, Renouard A, Tillement J P
Service Hospitalo-Universitaire de Pharmacologie, Centre Hospitalier Intercommunal de Créteil, France.
J Neurochem. 1988 Aug;51(2):421-5. doi: 10.1111/j.1471-4159.1988.tb01055.x.
Brain extraction of a tricyclic antidepressant, imipramine, was investigated using the carotid injection technique in the rat. The extent to which drug binding to plasma proteins and erythrocytes could inhibit the brain extraction was measured. Equilibrium dialysis showed that imipramine is highly bound to human serum albumin (HSA), alpha 1-acid glycoprotein (AAG), lipoproteins, and erythrocytes. The free dialyzable drug fraction was inversely related to the protein concentration. Despite this degree of binding, no significant reduction in the brain extraction of the drug was observed in the presence of HSA, lipoprotein, or erythrocytes. Only AAG reduced the brain transport of this drug in a ratio related to the protein concentration. However, the rat brain extraction was higher than expected from the in vitro measurement of the dialyzable fraction. These data indicate that the amount of circulating imipramine available for penetration in brain exceeds widely the dialyzable fraction of the drug as measured in vitro.
利用颈动脉注射技术在大鼠身上研究了三环类抗抑郁药丙咪嗪的脑摄取情况。测定了药物与血浆蛋白和红细胞结合对脑摄取的抑制程度。平衡透析表明，丙咪嗪与人类血清白蛋白（HSA）、α1-酸性糖蛋白（AAG）、脂蛋白和红细胞高度结合。可自由透析的药物分数与蛋白质浓度呈负相关。尽管存在这种结合程度，但在有HSA、脂蛋白或红细胞的情况下，未观察到药物脑摄取有显著降低。只有AAG以与蛋白质浓度相关的比例降低了该药物的脑转运。然而，大鼠脑摄取高于根据体外可透析分数测量所预期的值。这些数据表明，可用于穿透进入脑内的循环丙咪嗪量远远超过体外测量的药物可透析分数。
