Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
Br J Pharmacol. 2012 Jan;165(2):289-312. doi: 10.1111/j.1476-5381.2011.01557.x.
The drug efflux pump P-glycoprotein (P-gp) plays an important role in the function of the blood-brain barrier by selectively extruding certain endogenous and exogenous molecules, thus limiting the ability of its substrates to reach the brain. Emerging evidence suggests that P-gp may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. Despite some inconsistency in the literature, clinical investigations of potential associations between functional single nucleotide polymorphisms in ABCB1, the gene which encodes P-gp, and antidepressant response have highlighted a potential link between P-gp function and treatment-resistant depression (TRD). Therefore, co-administration of P-gp inhibitors with antidepressants to patients who are refractory to antidepressant therapy may represent a novel therapeutic approach in the management of TRD. Furthermore, certain antidepressants inhibit P-gp in vitro, and it has been hypothesized that inhibition of P-gp by such antidepressant drugs may play a role in their therapeutic action. The present review summarizes the available in vitro, in vivo and clinical data pertaining to interactions between antidepressant drugs and P-gp, and discusses the potential relevance of these interactions in the treatment of depression.
药物外排泵 P-糖蛋白（P-gp）通过选择性地将某些内源性和外源性分子排出，从而限制其底物到达大脑的能力，在血脑屏障的功能中发挥着重要作用。新出现的证据表明，P-gp 可能会限制几种抗抑郁药进入大脑的摄取，从而导致当前抗抑郁治疗成功率低。尽管文献中存在一些不一致，但对 ABCB1 基因（编码 P-gp）中功能性单核苷酸多态性与抗抑郁反应之间潜在关联的临床研究强调了 P-gp 功能与治疗抵抗性抑郁症（TRD）之间的潜在联系。因此，对于对抗抑郁治疗无反应的患者，将 P-gp 抑制剂与抗抑郁药联合给药可能代表治疗 TRD 的一种新的治疗方法。此外，某些抗抑郁药在体外抑制 P-gp，并且有人假设此类抗抑郁药物对 P-gp 的抑制可能在其治疗作用中发挥作用。本综述总结了有关抗抑郁药与 P-gp 之间相互作用的现有体外、体内和临床数据，并讨论了这些相互作用在抑郁症治疗中的潜在相关性。
