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关于促智药奥拉西坦在大脑中的生化研究。

Biochemical studies on the nootropic drug, oxiracetam, in brain.

作者信息

Trovarelli G, Gaiti A, De Medio G E, Brunetti M, Porcellati G

出版信息

Clin Neuropharmacol. 1986;9 Suppl 3:S56-64.

PMID:3594457
Abstract

The aim of this work was to study the effects of the nootropic drug oxiracetam, on lipid metabolism in rat brain. Twenty-month-old rats and spontaneous hypertensive (SHR) rats with cerebrovascular lesions were used, which showed an impaired learning and memory rate if challenged with behavioral tests. Oxiracetam improves the in vitro and in vivo synthesis of phosphatidylcholine (PhC) and phosphatidylethanolamine (PhE) impaired by aging, when respectively added to the incubation medium or administered subacutely to animals. SHR rats drinking saline, and with cerebrovascular lesions, have a reduced choline incorporation into cerebral phospholipids and an increase of arachidonic acid release from the same lipids if compared to SHR rats (without cerebrovascular lesions) drinking water. They also show a decreased incorporation rate of arachidonic acid into PhC, PhE, and PhC plasmalogen and PhE plasmalogen. If oxiracetam is chronically administered (200 mg/kg/day for 14 weeks) a significant variation in the incorporation of both precursors takes place. In the first 2 h after the intracerebroventricular (i.c.v.) injection of choline and arachidonic acid the values are comparable to those observed in SHR rats with lesions; at longer time intervals, however, the rates of incorporation are similar and even better than those of SHR rats without lesions. Since the drug does not seem to influence the incorporation of the precursors in the first 2 h after their administration, we may assume that oxiracetam acts on the turnover of the phospholipids more than on their rate of synthesis from injected precursors.

摘要

这项工作的目的是研究促智药奥拉西坦对大鼠脑脂质代谢的影响。使用了20月龄大鼠和患有脑血管病变的自发性高血压(SHR)大鼠,这些大鼠在接受行为测试时表现出学习和记忆率受损。当分别添加到孵育培养基中或对动物进行亚急性给药时,奥拉西坦可改善因衰老而受损的磷脂酰胆碱(PhC)和磷脂酰乙醇胺(PhE)的体外和体内合成。与饮用自来水的SHR大鼠(无脑血管病变)相比,饮用盐水且患有脑血管病变的SHR大鼠脑磷脂中胆碱掺入减少,相同脂质中花生四烯酸释放增加。它们还显示花生四烯酸掺入PhC、PhE、PhC缩醛磷脂和PhE缩醛磷脂的速率降低。如果长期给予奥拉西坦(200mg/kg/天,持续14周),两种前体的掺入都会发生显著变化。在脑室内(i.c.v.)注射胆碱和花生四烯酸后的最初2小时内,其值与患有病变的SHR大鼠中观察到的值相当;然而,在更长的时间间隔内,掺入率相似,甚至优于无病变的SHR大鼠。由于该药物在给药后的最初2小时内似乎不影响前体的掺入,我们可以假设奥拉西坦对磷脂周转的作用大于对其由注射前体合成速率的作用。

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