Inhibition of P-glycoprotein enhances transport of imipramine across the blood-brain barrier: microdialysis studies in conscious freely moving rats (original) (raw)

Abstract

Recent studies indicate that efflux of antidepressants by the multidrug resistance transporter P-glycoprotein (P-gp) at the blood-brain barrier (BBB) may contribute to treatment-resistant depression (TRD) by limiting intracerebral antidepressant concentrations. In addition, clinical experience shows that adjunctive treatment with the P-gp inhibitor verapamil may improve the clinical outcome in TRD. Therefore, the present study aimed to investigate the effect of P-gp inhibition on the transport of the tricyclic antidepressant imipramine and its active metabolite desipramine across the BBB.

Loading...

Loading Preview

Sorry, preview is currently unavailable. You can download the paper by clicking the button above.

References (59)

  1. Alexander SPH, Mathie A, Peters JA (2011). Guide to Receptors and Channels (GRAC), 5 th Edition. Br J Pharmacol 164 (Suppl. 1): S1-S324.
  2. Auguet M, Delaflotte S, Clostre F, Defeudis FV (1986). Verapamil as an apparent competitive antagonist of the serotonin receptor of rabbit isolated aorta. Gen Pharmacol 17: 133-135.
  3. Backman JT, Olkkola KT, Aranko K, Himberg JJ, Neuvonen PJ (1994). Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br J Clin Pharmacol 37: 221-225.
  4. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W (2007). Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology 52: 333-346.
  5. Bart J, Willemsen AT, Groen HJ, van der Graaf WT, Wegman TD, Vaalburg W et al. (2003). Quantitative assessment of P-glycoprotein function in the rat blood-brain barrier by distribution volume of [11C]verapamil measured with PET. Neuroimage 20: 1775-1782.
  6. Baumert C, Hilgeroth A (2009). Recent advances in the development of P-gp inhibitors. Anticancer Agents Med Chem 9: 415-436.
  7. Bungay PM, Morrison PF, Dedrick RL (1990). Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro. Life Sci 46: 105-119.
  8. Cascorbi I (2006). Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs. Pharmacol Ther 112: 457-473.
  9. Clarke G, O'Mahony SM, Cryan JF, Dinan TG (2009). Verapamil in treatment resistant depression: a role for the P-glycoprotein transporter? Hum Psychopharmacol 24: 217-223.
  10. Colabufo NA, Berardi F, Cantore M, Contino M, Inglese C, Niso M et al. (2010). Perspectives of P-glycoprotein modulating agents in oncology and neurodegenerative diseases: pharmaceutical, biological, and diagnostic potentials. J Med Chem 53: 1883-1897.
  11. Cole SPC, Loe DW, Deeley RG (2000). Verapamil stimulates glutathione transport by the 190-kDa multidrug resistance protein 1 (MRP1). J Pharmacol Exp Ther 293: 530-538.
  12. Cordoncardo C, O'Brien JP, Casals D, Rittmangrauer L, Biedler JL, Melamed MR et al. (1989). Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial-cells at blood-brain barrier sites. Proc Natl Acad Sci U S A 86: 695-698.
  13. BJP P-gp inhibition enhances imipramine BBB transport British Journal of Pharmacology (2012) 166 1333-1343 1341
  14. Ejsing TB, Linnet K (2005). Influence of P-glycoprotein inhibition on the distribution of the tricyclic antidepressant nortriptyline over the blood-brain barrier. Hum Psychopharmacol 20: 149-153.
  15. Ejsing TB, Hasselstrom J, Linnet K (2006). The influence of P-glycoprotein on cerebral and hepatic concentrations of nortriptyline and its metabolites. Drug Metabol Drug Interact 21: 139-162.
  16. Evrard PA, Ragusi C, Boschi G, Verbeeck RK, Scherrmann JM (1998). Simultaneous microdialysis in brain and blood of the mouse: extracellular and intracellular brain colchicine disposition. Brain Res 786: 122-127.
  17. Faassen F, Vogel G, Spanings H, Vromans H (2003). Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm 263: 113-122.
  18. Fleishaker JC, Sisson TA, Carel BJ, Azie NE (2000). Pharmacokinetic interaction between verapamil and almotriptan in healthy volunteers. Clin Pharmacol Ther 67: 498-503.
  19. Frahnert C, Rao ML, Grasmader K (2003). Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring. J Chromatogr B Analyt Technol Biomed Life Sci 794: 35-47.
  20. Friedl W, Propping P (1984). 3H-imipramine binding in human platelets: a study in normal twins. Psychiatry Res 11: 279-285.
  21. Gex-Fabry M, Eap CB, Oneda B, Gervasoni N, Aubry JM, Bondolfi G et al. (2008). CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit 30: 474-482.
  22. Hammarlund-Udenaes M (2010). Active-site concentrations of chemicals -are they a better predictor of effect than plasma/organ/tissue concentrations? Basic Clin Pharmacol Toxicol 106: 215-220.
  23. Heiser A (2007). Rat Jugular Vein and Carotid Artery Catheterization for Acute Survival Studies: A Practical Guide, 1st edn. Springer: New York.
  24. Hermann DJ, Krol TF, Dukes GE, Hussey EK, Danis M, Han YH et al. (1992). Comparison of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine. J Clin Pharmacol 32: 176-183.
  25. Hsiao P, Bui T, Ho RJ, Unadkat JD (2008). In vitro-to-in vivo prediction of P-glycoprotein-based drug interactions at the human and rodent blood-brain barrier. Drug Metab Dispos 36: 481-484.
  26. Huang C, Yoshimoto M, Miki K, Johns EJ (2006). The contribution of brain angiotensin II to the baroreflex regulation of renal sympathetic nerve activity in conscious normotensive and hypertensive rats. J Physiol 574: 597-604.
  27. Kantola T, Kivisto KT, Neuvonen PJ (1998). Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 64: 177-182.
  28. Kato M, Fukuda T, Serretti A, Wakeno M, Okugawa G, Ikenaga Y et al. (2008). ABCB1 (MDR1) gene polymorphisms are associated with the clinical response to paroxetine in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32: 398-404.
  29. Kovarik JM, Beyer D, Bizot MN, Jiang Q, Allison MJ, Schmouder RL (2005). Pharmacokinetic interaction between verapamil and everolimus in healthy subjects. Br J Clin Pharmacol 60: 434-437.
  30. Kwan P, Sills GJ, Butler E, Gant TW, Brodie MJ (2003). Differential expression of multidrug resistance genes in naive rat brain. Neurosci Lett 339: 33-36.
  31. de Lange EC, de Bock G, Schinkel AH, de Boer AG, Breimer DD (1998). BBB transport and P-glycoprotein functionality using MDR1A (-/-) and wild-type mice. Total brain versus microdialysis concentration profiles of rhodamine-123. Pharm Res 15: 1657-1665.
  32. de Lange ECM, de Boer AG, Breimer DD (2000). Methodological issues in microdialysis sampling for pharmacokinetic studies. Adv Drug Deliv Rev 45: 125-148.
  33. Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP et al. (1993). Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol 43: 827-832.
  34. Lin KM, Chiu YF, Tsai IJ, Chen CH, Shen WW, Liu SC et al. (2011). ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. Pharmacogenet Genomics 21: 163-170.
  35. Liow JS, Lu S, McCarron JA, Hong J, Musachio JL, Pike VW et al. (2007). Effect of a P-glycoprotein inhibitor, Cyclosporin A, on the disposition in rodent brain and blood of the 5-HT1A receptor radioligand, [11C](R)-(-)-RWAY. Synapse 61: 96-105.
  36. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ et al. (2002). Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 303: 1029-1037.
  37. Mason BL, Thomas SA, Lightman SL, Pariante CM (2011). Desipramine treatment has minimal effects on the brain accumulation of glucocorticoids in P-gp-deficient and wild-type mice. Psychoneuroendocrinology 36: 1351-1360.
  38. Nikisch G, Eap CB, Baumann P (2008). Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacol Res 58: 344-347.
  39. O'Brien FE, Dinan TG, Griffin BT, Cryan JF (2012). Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: clinical significance of in vitro and in vivo findings. Br J Pharmacol 165: 289-312.
  40. Page ME, Lucki I (2002). Effects of acute and chronic reboxetine treatment on stress-induced monoamine efflux in the rat frontal cortex. Neuropsychopharmacology 27: 237-247.
  41. Page ME, Bao L, Andre P, Pelta-Heller J, Sluzas E, Gonzalez-Alegre P et al. (2010). Cell-autonomous alteration of dopaminergic transmission by wild type and mutant (DeltaE) TorsinA in transgenic mice. Neurobiol Dis 39: 318-326.
  42. Pariante CM, Kim RB, Makoff A, Kerwin RW (2003). Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters. Br J Pharmacol 139: 1111-1118.
  43. Pariante CM, Thomas SA, Lovestone S, Makoff A, Kerwin RW (2004). Do antidepressants regulate how cortisol affects the brain? Psychoneuroendocrinology 29: 423-447.
  44. Pauwels EKJ, Erba P, Mariani G, Gomes CMF (2007). Multidrug resistance in cancer: its mechanism and its modulation. Drug News Perspect 20: 371-377.
  45. Paxinos G, Watson C (1998). The Rat Brain in Stereotaxic Coordinates, 4th edn. Academic Press: San Diego.
  46. Polasek TM, Elliot DJ, Lewis BC, Miners JO (2004). Mechanism- based inactivation of human cytochrome P4502C8 by drugs in vitro. J Pharmacol Exp Ther 311: 996-1007.
  47. Ravindranath V (1998). Metabolism of xenobiotics in the central nervous system: implications and challenges. Biochem Pharmacol 56: 547-551.
  48. Sarginson JE, Lazzeroni LC, Ryan HS, Ershoff BD, Schatzberg AF, Murphy GM (2010). ABCB1 (MDR1) polymorphisms and antidepressant response in geriatric depression. Pharmacogenet Genomics 20: 467-475.
  49. Sato Y, Shibanoki S, Sugahara M, Ishikawa K (1994). Measurement and pharmacokinetic analysis of imipramine and its metabolite by brain microdialysis. Br J Pharmacol 112: 625-629.
  50. Sawchuk RJ, Elmquist WF (2000). Microdialysis in the study of drug transporters in the CNS. Adv Drug Deliv Rev 45: 295-307.
  51. Siddiqui A, Kerb R, Weale ME, Brinkmann U, Smith A, Goldstein DB et al. (2003). Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 348: 1442-1448.
  52. Syvanen S, Blomquist G, Sprycha M, Hoglund AU, Roman M, Eriksson O et al. (2006). Duration and degree of cyclosporin induced P-glycoprotein inhibition in the rat blood-brain barrier can be studied with PET. Neuroimage 32: 1134-1141.
  53. Thrivikraman KV, Huot RL, Plotsky PM (2002). Jugular vein catheterization for repeated blood sampling in the unrestrained conscious rat. Brain Res Brain Res Protoc 10: 84-94.
  54. Tsai TH, Liu SC, Tsai PL, Ho LK, Shum AY, Chen CF (2002). The effects of the cyclosporin A, a P-glycoprotein inhibitor, on the pharmacokinetics of baicalein in the rat: a microdialysis study. Br J Pharmacol 137: 1314-1320.
  55. Uhr M, Grauer MT, Holsboer F (2003). Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. Biol Psychiatry 54: 840-846.
  56. Uhr M, Tontsch A, Namendorf C, Ripke S, Lucae S, Ising M et al. (2008). Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron 57: 203-209.
  57. Wang YH, Jones DR, Hall SD (2004). Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos 32: 259-266.
  58. Xie R, Hammarlund-Udenaes M, de Boer AG, de Lange EC (1999). The role of P-glycoprotein in blood-brain barrier transport of morphine: transcortical microdialysis studies in mdr1a (-/-) and mdr1a (+/+) mice. Br J Pharmacol 128: 563-568.
  59. Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH et al. (2001). In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther 296: 723-735.