Goldberg M A, Todoroff T
Neurology. 1980 Aug;30(8):826-31. doi: 10.1212/wnl.30.8.826.
We investigated the binding of radioactive carbamazepine and valproic acid to brain homogenates, lipid-free extracts, brain lipid, and phospholipid fractions. Carbamazepine was bound to each of these components in a manner that is qualitatively indistinguishable from the binding of phenytoin, in spite of major physical-chemical differences in these molecules but consistent with the similarities in pharmacologic action. These data support the concept that protein and phospholipid binding may be required for the activity of membrane-stabilizing anticonvulsants. Neither valproic acid nor its metabolites exhibited binding to brain or to any of the individual components tested. Therefore, binding cannot explain the reported long duration of action of this drug.
我们研究了放射性卡马西平和丙戊酸与脑匀浆、脱脂提取物、脑脂质及磷脂组分的结合情况。尽管这些分子在物理化学性质上存在重大差异，但卡马西平与这些组分中的每一种的结合方式在定性上与苯妥英的结合无法区分，不过这与它们在药理作用上的相似性是一致的。这些数据支持了这样一种观点，即膜稳定抗惊厥药物的活性可能需要蛋白质和磷脂结合。丙戊酸及其代谢产物均未显示与脑或所测试的任何单个组分有结合。因此，结合不能解释该药物所报道的长效作用。
