Neuropharmacodynamic evaluation of the centrally active thyrotropin-releasing hormone analogue [Leu2]TRH and its chemical brain-targeting system.
Neuropharmacodynamic evaluation of the centrally active thyrotropin-releasing hormone analogue [Leu2]TRH and its chemical brain-targeting system.
复制标题
中枢活性促甲状腺素释放激素类似物 [Leu2]TRH 及其化学脑靶向系统的神经药效学评估。
DOI：
10.1016/s0006-8993(02)03251-1
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发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Zharikova,AlevtinaD
中科院分区：
文献类型：
--
作者：
Prokai,Laszlo;Zharikova,AlevtinaD
中枢活性促甲状腺激素释放激素（TRH）类似物pGlu-Leu-Pro-NH 2（[Leu 2]TRH）在其灌注到大鼠海马的过程中表现出细胞外乙酰胆碱浓度的显著增加，并且当通过体内颅内微透析测量时，与TRH相比，这种效应在递送更少量的类似物时表现出来。通过使用脑靶向衍生物增强[Leu 2]TRH在静脉内给药后的神经药效学功效，其中成熟肽的祖序列嵌入分子结构中，促进增强的脑递送、保留和原位生成的促肾上腺皮质激素活性分子。与未修饰的肽相比，靶向系统显著改善了大鼠细胞外乙酰胆碱水平的治疗累积效应。
The centrally active thyrotropin-releasing hormone (TRH) analogue pGlu–Leu–Pro–NH2([Leu2]TRH) showed a significant increase in the extracellular acetylcholine concentration during its perfusion to the hippocampus in rats, and this effect was manifested upon the delivery of the analogue in much smaller quantities compared to TRH when measured by in vivo intracranial microdialysis. The neuropharmacodynamic efficacy of [Leu2]TRH upon intravenous administration was augmented by the use of a brain-targeting derivative in which the progenitor sequence of the mature peptide was embedded in a molecular architecture that promoted enhanced brain delivery, retention and in situ generation of the pharmacologically active molecule. Compared to the unmodified peptide, the targeting system significantly improved the cumulative effect of the treatment on extracellular acetylcholine levels in rats.