TY  - JOUR
  - O'Brien, FE,Clarke, G,Dinan, TG,Cryan, JF,Griffin, BT
  - 2013
  - November
  - International Journal of Neuropsychopharmacology
  - Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability
  - Validated
  - Altmetric: 1 ()
  - Antidepressant bidirectional transport study imipramine MDCKII-MDR1 P-glycoprotein CENTRAL-NERVOUS-SYSTEM TREATMENT-RESISTANT DEPRESSION IN-VITRO LIQUID-CHROMATOGRAPHY THERAPEUTIC RESPONSE EFFLUX TRANSPORTERS ANTIEPILEPTIC DRUGS CLINICAL-RESPONSE GENE DISRUPTION MDCK CELLS
  - 16
  - 2259
  - 2272
  - The pharmacological concept that inhibition of the drug efflux pump P-glycoprotein (P-gp) enhances brain distribution of the antidepressant imipramine in the rat has recently been demonstrated. To determine if these findings are relevant to humans, the present study investigated if imipramine is a transported substrate of human P-gp. Furthermore, additional experiments were carried out to determine if findings in relation to imipramine and human P-gp would apply to other antidepressants from a range of different classes. To this end, bidirectional transport experiments were carried out in the ABCB1-transfected MDCKII-MDR1 cell line. Transported substrates of human P-gp are subjected to net efflux in this system, exhibiting a transport ratio (TR) >= 1.5, and directional efflux is attenuated by co-incubation of a P-gp inhibitor. Imipramine was identified as a transported substrate of human P-gp (TR-1.68, attenuated by P-gp inhibition). However, the antidepressants amitriptyline, duloxetine, fluoxetine and mirtazapine were not transported substrates of human P-gp (TR <= 1.16 in all cases). These results offer insight into the role of P-gp in the distribution of antidepressants, revealing that rodent findings pertaining to imipramine may translate to humans. Moreover, the present results highlight that other antidepressants may not be transported substrates of human P-gp.
  - 10.1017/S1461145713000692
DA  - 2013/11
ER  - 

@article{V243939156,
   = {O'Brien,  FE and Clarke,  G and Dinan,  TG and Cryan,  JF and Griffin,  BT },
   = {2013},
   = {November},
   = {International Journal of Neuropsychopharmacology},
   = {Human P-glycoprotein differentially affects antidepressant drug transport: relevance to blood-brain barrier permeability},
   = {Validated},
   = {Altmetric: 1 ()},
   = {Antidepressant bidirectional transport study imipramine MDCKII-MDR1 P-glycoprotein CENTRAL-NERVOUS-SYSTEM TREATMENT-RESISTANT DEPRESSION IN-VITRO LIQUID-CHROMATOGRAPHY THERAPEUTIC RESPONSE EFFLUX TRANSPORTERS ANTIEPILEPTIC DRUGS CLINICAL-RESPONSE GENE DISRUPTION MDCK CELLS},
   = {16},
  pages = {2259--2272},
   = {{The pharmacological concept that inhibition of the drug efflux pump P-glycoprotein (P-gp) enhances brain distribution of the antidepressant imipramine in the rat has recently been demonstrated. To determine if these findings are relevant to humans, the present study investigated if imipramine is a transported substrate of human P-gp. Furthermore, additional experiments were carried out to determine if findings in relation to imipramine and human P-gp would apply to other antidepressants from a range of different classes. To this end, bidirectional transport experiments were carried out in the ABCB1-transfected MDCKII-MDR1 cell line. Transported substrates of human P-gp are subjected to net efflux in this system, exhibiting a transport ratio (TR) >= 1.5, and directional efflux is attenuated by co-incubation of a P-gp inhibitor. Imipramine was identified as a transported substrate of human P-gp (TR-1.68, attenuated by P-gp inhibition). However, the antidepressants amitriptyline, duloxetine, fluoxetine and mirtazapine were not transported substrates of human P-gp (TR <= 1.16 in all cases). These results offer insight into the role of P-gp in the distribution of antidepressants, revealing that rodent findings pertaining to imipramine may translate to humans. Moreover, the present results highlight that other antidepressants may not be transported substrates of human P-gp.}},
   = {10.1017/S1461145713000692},
  source = {IRIS}
}