Metting T L, Burgio D E, Terry A V, Beach J W, McCurdy C R, Allen D D
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo 79106-1712, USA.
Neurosci Lett. 1998 Dec 11;258(1):25-8. doi: 10.1016/s0304-3940(98)00871-4.
Delivery of certain compounds to brain is restricted by the nature of the blood-brain barrier (BBB). Many valuable pharmaceuticals are excluded from the CNS due to hydrophilicity or charge. These limitations have been overcome by numerous methods. One method we use is to take advantage of saturable nutrient transporters located at the barrier. These systems transport hydrophilic and charged nutrients into brain such as choline, a quaternized neurotransmitter precursor. Using knowledge of their substrate specificity, it is possible to deliver agents into brain using these nutrient carriers. In this report, derivatives of lobeline and isoarecolone were evaluated to determine if they may gain access to brain by the blood-brain barrier basic amine transporter using the in situ brain perfusion technique. These compounds do bind the blood-brain barrier basic amine transporter and may enter brain by this transport system.
某些化合物向大脑的递送受到血脑屏障（BBB）性质的限制。许多有价值的药物由于亲水性或带电性而被中枢神经系统排除在外。这些限制已通过多种方法得以克服。我们使用的一种方法是利用位于该屏障处的可饱和营养转运体。这些系统将亲水性和带电的营养物质转运到大脑中，例如胆碱，一种季铵化的神经递质前体。利用它们对底物特异性的了解，有可能使用这些营养载体将药物递送至大脑。在本报告中，使用原位脑灌注技术评估了洛贝林和异槟榔次碱的衍生物，以确定它们是否可以通过血脑屏障碱性胺转运体进入大脑。这些化合物确实与血脑屏障碱性胺转运体结合，并可能通过该转运系统进入大脑。
