Reinhart Walter H, Lubszky Szabina, Thöny Sandra, Schulzki Thomas
Department of Internal Medicine, Kantonsspital Graubünden, Chur, Switzerland.
Department of Internal Medicine, Kantonsspital Graubünden, Chur, Switzerland.
Toxicol In Vitro. 2014 Oct;28(7):1274-9. doi: 10.1016/j.tiv.2014.06.008. Epub 2014 Jul 2.
The normal red blood cell (RBC) shape is a biconcave discocyte. An intercalation of a drug in the outer half of the membrane lipid bilayer leads to echinocytosis, an intercalation in the inner half to stomatocytosis. We have used the shape transforming capacity of RBCs as a model to analyse the membrane interaction potential of various neurotropic drugs. Chlorpromazine, clomipramine, citalopram, clonazepam, and diazepam induced a reversible stomatocytosis, phenytoin induced echinocytosis, while the anticonvulsants levetiracetam, valproic acid and phenobarbital had no effect. This diversity of RBC shape transformations suggests that the pharmacological action is not linked to the membrane interaction. We conclude that this simple RBC shape transformation assay could be a useful tool to screen for potential drug interactions with cell membranes.
正常红细胞（RBC）的形状是双凹圆盘状。药物嵌入膜脂质双层的外半部分会导致棘形红细胞增多症，嵌入内半部分则会导致口形红细胞增多症。我们利用红细胞的形状转化能力作为模型来分析各种亲神经药物的膜相互作用潜力。氯丙嗪、氯米帕明、西酞普兰、氯硝西泮和地西泮可诱导可逆性口形红细胞增多症，苯妥英可诱导棘形红细胞增多症，而抗惊厥药左乙拉西坦、丙戊酸和苯巴比妥则无作用。红细胞形状转化的这种多样性表明药理作用与膜相互作用无关。我们得出结论，这种简单的红细胞形状转化试验可能是筛选潜在药物与细胞膜相互作用的有用工具。
