Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier
Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier
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DOI：
10.1023/a:1024960819430
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发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Takatori, T
中科院分区：
文献类型：
--
作者：
Sakurada, K;Matsubara, K;Takatori, T
采用大鼠在体脑微透析技术，采用高效液相色谱/紫外联用技术，测定了目前神经毒剂解毒剂治疗药物--碘解磷定(2-PAM)对血脑屏障的通透性。静脉注射2-PAM(10，50,100 mg/kg)后，透析液中出现剂量依赖性的2-PAM，50 mg/kg后1h纹状体细胞外/血浓度比值为0.093+/-0.053(均值+/-扫描电子显微镜)。这一发现为2-PAM的血脑屏障渗透提供了确凿的证据。我们还考察了2-PAM的血脑屏障穿透是否由特定的转运体介导，如中性或碱性氨基酸转运系统。虽然尚不清楚，但2-PAM的神经摄取依赖于Na+。2-PAM的平均血脑屏障渗透率约为10%，提示静脉注射2-PAM可能在一定程度上有效地重新激活被阻断的脑胆碱酯酶。
The in vivo rat brain microdialysis technique with HPLC/UV was used to determine the blood-brain barrier (BBB) penetration of pralidoxime iodide (2-PAM), which is a component of the current nerve agent antidote therapy. After intravenous dosage of 2-PAM (10, 50, 100 mg/kg), 2-PAM appeared dose-dependently in the dialysate; the striatal extracellular/blood concentration ratio at 1 h after 50 mg/kg dosage was 0.093 +/- 0.053 (mean +/- SEM). This finding offered conclusive evidence of the BBB penetration of 2-PAM. We also examined whether the BBB penetration of 2-PAM was mediated by a certain specific transporter, such as a neutral or basic amino acid transport system. Although it was unclear, the neural uptake of 2-PAM was Na+ dependent. The mean BBB penetration by 2-PAM was approximately 10%, indicating the intravenous administration of 2-PAM might be to a degree effective to reactivation of the blocked cholinesterase in the brain.