尼古丁的N-甲基季铵化消除了血脑屏障的穿透作用。
Blood-brain barrier penetration abolished by N-methyl quaternization of nicotine.
作者信息
Oldendorf W H, Stoller B E, Harris F L
机构信息
Department of Veterans Affairs, West Los Angeles Medical Center, CA 90073.
出版信息
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):307-11. doi: 10.1073/pnas.90.1.307.
The present study determined the effect of organically quaternizing either of the two tertiary nitrogen sites of nicotine to assess the in vivo effects of the permanently ionized states of the synthesized N-[14C]methylnicotines on brain uptake in rat after intracarotid injection. Male Sprague-Dawley rats were used to measure the brain uptake index (BUI) by single-pass clearance in brain after rapid injection at pH 7.4 into the left common carotid artery (expressed as a percentage) relative to simultaneously injected 3HOH. The BUI of [14C]mannitol, a control for the method background, was measured to be 2.6 +/- 0.6. At physiological pH, in striking contrast to the [pyrrolidine-2-14C]nicotine BUI of 120 +/- 3, the N-[14C]-methylnicotines had a BUI of 3.0 +/- 0.6, which was not significantly different from the method background and which indicated abolition of blood-brain barrier penetration of nicotine with the sensitivity of the BUI method.
本研究通过对尼古丁两个叔氮位点之一进行有机季铵化，来评估合成的N-[¹⁴C]甲基烟碱的永久离子化状态对大鼠经颈内动脉注射后脑中摄取的体内效应。雄性Sprague-Dawley大鼠用于通过在pH 7.4条件下快速注射到左颈总动脉后脑中的单通道清除率来测量脑摄取指数（BUI，以百分比表示），相对于同时注射的³H-OH。作为方法背景对照的[¹⁴C]甘露醇的BUI经测量为2.6±0.6。在生理pH值下，与[吡咯烷-2-¹⁴C]尼古丁的BUI为120±3形成鲜明对比的是，N-[¹⁴C]甲基烟碱的BUI为3.0±0.6，这与方法背景无显著差异，表明BUI方法的敏感性显示尼古丁的血脑屏障穿透被消除。
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