硝基苄基硫代肌苷在大鼠体内穿越血脑屏障的能力。

Ability of nitrobenzylthioinosine to cross the blood-brain barrier in rats.

作者信息

Anderson C M, Sitar D S, Parkinson F E

机构信息

Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.

出版信息

Neurosci Lett. 1996 Nov 29;219(3):191-4. doi: 10.1016/s0304-3940(96)13220-1.

DOI:10.1016/s0304-3940(96)13220-1

PMID:8971812

Abstract

Nucleoside transport inhibitors that cross the blood-brain barrier may be able to potentiate the neuroprotective effects of adenosine. We tested whether nitrobenzylthioinosine (NBMPR) crosses the blood-brain barrier in three types of experiments. First, intravenous injection of [3H]NBMPR and [14C]sucrose was performed. Brain volume of distribution and brain delivery were greater for [3H]NBMPR than for [14C]sucrose. Second, rats were injected intraperitoneally with NBMPR 5'-monophosphate (NBMPR-P), a prodrug form of NBMPR, or vehicle. Perchloric acid extracts of brains from rats treated with NBMPR-P inhibited [3H]NBMPR binding in competition binding assays nearly 3-fold more than extracts from brains of vehicle-treated animals. Third, cerebrospinal fluid (CSF) extracted from rats treated with NBMPR-P (10 mg/kg i.p.) contained 24.1 +/- 4.4 nM NBMPR while levels were undetectable in CSF from vehicle-treated rats. From these data, we conclude that NBMPR crosses the blood-brain barrier.

摘要

能够穿过血脑屏障的核苷转运抑制剂或许能够增强腺苷的神经保护作用。我们通过三类实验测试了硝基苄基硫代肌苷（NBMPR）是否能穿过血脑屏障。首先，进行了[³H]NBMPR和[¹⁴C]蔗糖的静脉注射。[³H]NBMPR的脑分布容积和脑递送量比[¹⁴C]蔗糖更大。其次，给大鼠腹腔注射NBMPR的前药形式——NBMPR 5'-单磷酸酯（NBMPR-P）或赋形剂。在竞争结合试验中，用NBMPR-P处理的大鼠脑的高氯酸提取物对[³H]NBMPR结合的抑制作用比用赋形剂处理的动物脑提取物强近3倍。第三，从用NBMPR-P（10毫克/千克腹腔注射）处理的大鼠中提取的脑脊液（CSF）含有24.1±4.4纳摩尔的NBMPR，而在赋形剂处理的大鼠的脑脊液中未检测到该水平。根据这些数据，我们得出结论，NBMPR能穿过血脑屏障。