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美西多宁和赛马克的抗缺氧及抗遗忘作用

[Antihypoxic and antiamnesic effects of mexidol and semax].

作者信息

Iasnetsov Vik V, Voronina T A

出版信息

Eksp Klin Farmakol. 2010 Apr;73(4):2-7.

Abstract

Upon single administration, mexidol and semax only in doses of 100 and 0.05 mg/kg, respectively, produced an antihypoxic effect on mice in the altitude chamber and hermetic chamber tests. Preventive course administration of mexidol and semax for 6 days gave significant antihypoxic effect on the model of acute hypobaric hypoxia in mice in doses of 75 and 0.1 mg/kg per day, respectively, in which the same preparations upon single administration were ineffective. Neither mexidol nor semax upon single administration were effective on the models of acute hemic and histotoxic hypoxia. On various models of amnesia (except that induced by the maximal electroshock) in mice, both mexidol and semax exhibited marked antiamnesic effects comparable with that of the reference nootrope drugs piracetam and oxyracetam. Mexidol showed a linear, while semax exhibited a bell-shaped reversible dose-effect relationships. Mexidol and semax inhibited the ortho- and antidromic population response spikes of CA1 pyramidal neurons of survival hippocampal slices in rats. It was estimated that mexidol (in contrast to semax) increased oxygen consumption in rat brain mitochondria and had a linear dose-effect relationship in a concentration range of 1-5 mM. It is concluded that mexidol should be used in high doses (for both single and course administration) for obtaining antihypoxic and antiamnesic effects, while semax requires a thoroughly controlled choice of dosage.

摘要

单次给药时,美西多宁和塞马通分别仅在100和0.05毫克/千克的剂量下,在高原舱和密封舱试验中对小鼠产生抗缺氧作用。美西多宁和塞马通预防性连续给药6天,分别以每天75和0.1毫克/千克的剂量,对小鼠急性低压缺氧模型产生显著的抗缺氧作用,而相同制剂单次给药无效。美西多宁和塞马通单次给药对急性血液性和组织中毒性缺氧模型均无效。在小鼠的各种失忆模型(除最大电休克诱导的模型外)中,美西多宁和塞马通均表现出与参比益智药吡拉西坦和奥拉西坦相当的显著抗失忆作用。美西多宁呈现线性,而塞马通呈现钟形可逆剂量效应关系。美西多宁和塞马通抑制大鼠存活海马切片CA1锥体神经元的正向和逆向群体反应峰电位。据估计,美西多宁(与塞马通不同)增加大鼠脑线粒体的氧消耗,并且在1 - 5毫摩尔的浓度范围内具有线性剂量效应关系。得出的结论是,为获得抗缺氧和抗失忆作用,美西多宁应大剂量使用(单次和连续给药均如此),而塞马通需要严格控制剂量选择。

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