Lopez G-Coviella I, Agut J, Von Borstel R, Wurtman R J
Laboratory of Neuroendocrine Regulation, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A.
Neurochem Int. 1987;11(3):293-7. doi: 10.1016/0197-0186(87)90049-0.
We examined the effects of cytidine (5?)-diphosphocholine (CDP-choline) on plasma levels of cytidine, choline, and unchanged CDP-choline among normal volunteers receiving the substance orally or intravenously, and rats receiving it intravenously. Two hours after a single oral dose (2g), plasma choline levels were increased by 48% and plasma cytidine by 136%. Among subjects receiving three doses (2g each) at two-hour intervals, plasma choline peaked (30% over baseline) 4 h after the initial CDP-choline dose, while plasma cytidine levels continued to increase for at lest 6 h, at which time they were five times basal levels (P < 0.01). Intravenously-administered CDP-choline was rapidly hydrolysed, in both the human and the rat. In humans given the CDP-choline by infusion over 30 min, plasma CDP-choline fell to undetectable levels almost immediately after the end of the infusion period; plasma choline and cytidine peaked at that time, but their concentrations remained significantly elevated for at least 6 h. In rats given a bolus injection of CDP-choline, five minutes earlier, the unchanged compound was also undetectable in plasma, while plasma cytidine levels increased markedly and remained elevated for at least 60 min. These observations show that CDP-choline is converted to at least two major circulating metabolites, choline and cytidine. Since both of these compounds are used in the biosynthesis of phosphatidylcholine, both may be involved in the long-term effects of the CDP-choline.
我们研究了胞苷（5′）-二磷酸胆碱（CDP-胆碱）对口服或静脉给予该物质的正常志愿者以及静脉给予该物质的大鼠血浆中胞苷、胆碱和未改变的CDP-胆碱水平的影响。单次口服剂量（2g）后两小时，血浆胆碱水平升高了48%，血浆胞苷升高了136%。在每隔两小时接受三剂（每剂2g）的受试者中，血浆胆碱在初始CDP-胆碱剂量后4小时达到峰值（比基线高30%），而血浆胞苷水平至少持续升高6小时，此时是基础水平的五倍（P<0.01）。静脉给予的CDP-胆碱在人和大鼠体内均迅速水解。在30分钟内输注CDP-胆碱的人体中，输注期结束后血浆CDP-胆碱几乎立即降至检测不到的水平；血浆胆碱和胞苷在此时达到峰值，但它们的浓度至少在6小时内仍显著升高。在5分钟前给予CDP-胆碱推注的大鼠中，血浆中也检测不到未改变的化合物，而血浆胞苷水平显著升高并至少持续升高60分钟。这些观察结果表明，CDP-胆碱可转化为至少两种主要的循环代谢物，即胆碱和胞苷。由于这两种化合物都用于磷脂酰胆碱的生物合成，它们可能都参与了CDP-胆碱的长期作用。
