Vasil'eva E V, Kondrakhin E A, Salimov R M, Kovalev G I
Eksp Klin Farmakol. 2016;79(9):3-11.
Pharmacological effects of intraperitoneal (i.p.) and intranasal (i.n.) administration of heptapeptide selank (300 μg/kg/day for 5 days), known to possess anxiolytic and nootropic properties, were compared by studying the elevated-plus-maze behavior of inbred BALB/c and C57BL/6 mice and measuring the binding of markers to NMDA and GABA receptors of brain. The anxiolytic and nootropic efficiency of selank administered via both routes was observed only in BALB/c mice, which were characterized by initially reduced exploratory activity and higher levels of anxiety as compared to C57BL/6 mice. In BALB/c mice, i.p. selank increased the number of [G-(3)H]SR 95531 binding sites with GABA-receptors in the frontal cortex by 38%, without change in binding to NMDA receptors in the hippocampus. On the contrary, i.n. selank led to an increase in the density of [G-(3)H]MK-801 binding sites by 23% with no effect on GABA receptors. It is suggested that the differences in pharmacological spectra observed for the two routes of selank administration are determined by specific features of drug pharmacokinetics and biotransformation as well as by the dynamics of formation of the anxiolytic and nootropic effects of selank.
已知具有抗焦虑和益智特性的七肽selank经腹腔注射（i.p.）和鼻内给药（i.n.）（300μg/kg/天，持续5天）的药理作用，通过研究近交系BALB/c和C57BL/6小鼠在高架十字迷宫中的行为以及测量标记物与脑NMDA和GABA受体的结合来进行比较。仅在BALB/c小鼠中观察到通过两种途径给药的selank的抗焦虑和益智效果，与C57BL/6小鼠相比，BALB/c小鼠的特点是初始探索活动减少且焦虑水平较高。在BALB/c小鼠中，腹腔注射selank使额叶皮质中与GABA受体结合的[G-(3)H]SR 95531结合位点数量增加38%，而海马体中与NMDA受体的结合无变化。相反，鼻内给药selank导致[G-(3)H]MK-801结合位点密度增加23%，对GABA受体无影响。提示selank两种给药途径所观察到的药理谱差异是由药物药代动力学和生物转化的特定特征以及selank抗焦虑和益智作用形成的动力学所决定的。
