【作者】 王丹； 张继伟； 徐四川；

【Author】 Dan WANG;Jiwei ZHANG;Sichuan XU;Key Laboratory of Education Ministry for Medicinal Chemistry of Natural Resource, College of Chemical Science and Technology, Yunnan University;Center for Certification & Evaluation,Yunnan food and Drug Administration;

【机构】 云南大学化学科学与工程学院,自然资源药物化学教育部重点实验室； 云南省食品药品监督管理局药品认证审评中心；

【摘要】 苯丙胺具有中枢兴奋作用,作为多巴胺受体激动剂,能够促进多巴胺的释放,产生各种生理功能、依赖和危害,因其具有成瘾性,而被列为毒品。毒品分子功能和成瘾机制,涉及毒品分子透过细胞膜的能力和在细胞膜中间层自由扩散运动的特性,因为只有进入到细胞膜内部的毒品分子才能通过多巴胺分子通道发挥其功能作用1-2。本文通过分子动力学模拟的方法(gromacs程序),获得苯丙胺在1-棕榈酰-2-油酰-卵磷脂(POPC)双层膜中和透过膜的运动自由能变化和运动轨迹3-4,初步探索了苯丙胺在POPC磷脂双层膜中扩散和透过过程的运动机制。苯丙胺分子在POPC磷脂双层膜中做扩散运动的自由能变化约为30 kJ·mol-1,显示苯丙胺分子在细胞膜中层很容易横向或纵向扩散。模拟获得的苯丙胺透过POPC双层膜的自由能垒比较低,因此我们从自由能垒角度上阐明苯丙胺分子具有透过细胞膜运动的特性,促进理解苯丙胺分子成瘾机制。更多还原

【Abstract】 Benzedrine, as an activator of dopamine, can promote the releasing of functioning dopamine and cause multiple physiological functions, dependence and harms, and therefore it has been listed as an addiction drug. The addiction mechanism is associated with its ability of diffusion within and permeation through cell membrane, because only after the drug molecule locates inside cell, it can play its role in releasing dopamine through dopamine molecule channel. In present work, by using molecular dynamics simulations based on gromacs programs we studied the ability of benzedrine diffusing within and permeating through a 1-palmitoyl-2-oleoyl-glycero-3-phosphatedylcholine(POPC) phospholipid bilayer membrane, to probe its addiction mechanism. The obtained lower free energy barrier for benzedrine to permeate through the POPC bilayer membrane suggests that it is capable of permeating through cell membrane. Therefore, our research work on the view of free energy barrier makes clear the capability for benzedrine to permeate through cell membrane easily, by which we can figure out and understand its addiction mechanism.更多还原