Agúndez José A G, Jiménez-Jiménez Félix J, Alonso-Navarro Hortensia, García-Martín Elena
Department of Pharmacology, University of Extremadura Cáceres, Spain ; ISCIII Research Network of Adverse Reactions to Allergens and Drugs Madrid, Spain.
Section of Neurology, Hospital Universitario del Sureste Madrid, Spain.
Front Cell Neurosci. 2014 Oct 17;8:335. doi: 10.3389/fncel.2014.00335. eCollection 2014.
Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB) has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to the BBB as a drug-metabolizing barrier. The presence of drug-metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.
药物生物转化是促进机体排出化学物质并降低其药理活性的关键机制。已发表的证据表明，脑内药物代谢可能在药物不良反应的发生以及药物和外源性物质的临床反应中发挥作用。血脑屏障（BBB）主要被视为药物和外源性物质的物理屏障，而作为药物代谢屏障的血脑屏障却很少受到关注。血脑屏障中存在药物代谢酶可能具有功能意义，因为局部代谢可能使药物失活，或改变药物穿越血脑屏障的能力，从而改变药物反应和发生药物不良反应的风险。在这篇观点论文中，我们讨论了脑和血脑屏障中相关外源性物质代谢酶的表达，并阐述了这些血脑屏障药物代谢酶作为药物反应调节剂的潜在作用的当前进展和未来方向。
