抗抑郁药进入细胞,器官和膜
Zack Blumenfeld1,2, Kallol Bera3, Eero Castrén4
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
概括
许多抗抑郁药对细胞内点起作用,挑战了关于细胞外药物作用的传统观点. 了解药物进入亚细胞区的运动是新型抗抑郁药开发的关键.
科学领域:
- 神经药理学神经药理学
- 药用化学 医学化学
- 药理动力学 药理动力学
背景情况:
- 主流的神经药理学范式假设药物点是细胞外的,位于血膜上.
- 然而,一些抗抑郁药通过细胞质或细胞器内的细胞内点发挥治疗作用.
- 这挑战了传统的理解,并需要探索在亚细胞区内的药物处置.
研究的目的:
- 审查管理药物进入亚细胞区的化学,药理动力学和药理动力学原则.
- 分析影响抗抑郁药物穿透膜和与细胞内标相互作用的特性.
- 讨论这些原则对理解抗抑郁药作用机制的含义,包括"位置偏差行为".
主要方法:
- 对抗抑郁药物的药理动力学和药理动力学现有文献的综述.
- 对LogP,pKa和LogDpH7.4等物理化学性质的分析,与膜透有关.
- 检查分布体积 (Vd) 和其细胞上和细胞下组成部分.
主要成果:
- 抗抑郁药物的作用可以在亚细胞区内开始,与细胞外向目标假设形成鲜明对比.
- 质子事件,电荷,疏水性 (LogP) 和脂质溶解性 (LogDpH7.4) 显著影响膜透.
- 一些抗抑郁药的大量分布 (Vd) 表明了大量的亚细胞分布,包括器官捕获.
结论:
- 了解抗抑郁药物进入亚细胞区的运动对于阐明它们的全部治疗机制至关重要.
- 物理化学性质和VD是药物达到细胞内点的能力的关键决定因素.
- "位置偏差作用"或"内外药理学"的概念为研究细胞内药物标提供了一个框架.
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