Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings.

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O'Brien FE, Dinan TG, Griffin BT, Cryan JF

Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings.

Br J Pharmacol. 2012 Jan;165(2):289-312. doi: 10.1111/j.1476-5381.2011.01557.x.

PubMed ID

21718296 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Desmethylsertraline	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Fluoxetine	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details