Future perspectives for brain pharmacotherapies: Implications of drug transport processes at the blood—brain barrier

Therapeutic Advances in Neurological Disorders

Volumn 1, Issue 3, 2008, Pages 167-179

  Hermann, Dirk M ^a  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

Author keywords

ABC transporter; Biodistribution; Pharmacology

Indexed keywords

EID: 84993790625     PISSN: 17562856     EISSN: None     Source Type: Journal    
DOI: 10.1177/1756285608097775     Document Type: Review

References (96)

1. Abbott, N.J., Rönnbäck, L. and Hansson, E. (2006) Astrocyte-endothelial interactions at the blood-brain barrier, Nat Rev Neurosci 7: 41-53.
2. Agrawal, M., Abraham, J., Balis, F.M., Edgerly, M., Stein, W.D., Bates, S. et al. (2003) Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576, Clin Cancer Res 9: 650-656.
3. Albers, G.W., Goldstein, L.B., Hall, D. and Lesko, L.M. (2001) Aptiganel Acute Stroke Investigators. Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial, JAMA 286: 2673-2682.
4. Bacigaluppi, M. and Hermann, D.M. (2008) New targets of neuroprotection in ischemic stroke, Scientific World Journal 8: 698-712.
5. Bacigaluppi, M., Pluchino, S., Martino, G., Kilic, E. and Hermann, D.M. (2008) Neural stem / precursor cells for the treatment of ischemic stroke, J Neurol Sci 265: 73-77.
6. Badan, I., Buchhold, B., Hamm, A., Gratz, M., Walker, L.C., Platt, D. et al. (2003) Accelerated glial reactivity to stroke in aged rats correlates with reduced functional recovery, J Cereb Blood Flow Metab 23: 845-854.
7. Baltes, S., Gastens, A.M., Fedrowitz, M., Potschka, H., Kaever, V. and Löscher, W. (2007) Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse p-glycoprotein, Neuropharmacology 52: 333-346.
8. Bauer, B., Hartz, A.M., Lucking, J.R., Yang, X., Pollack, G.M. and Miller, D.S. (2008) Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and phase-II metabolising enzyme, GSTpi, at the blood-brain barrier, J Cereb Blood Flow Metab 28: 1222-1234.
9. Begley, D.J. (2004) Delivery of therapeutic agents to the central nervous system: the problems and the possibilities, Pharmacol Ther 104: 29-45.
10. Bolhuis, H., van Veen, H.W., Molenaar, D., Poolman, B., Driessen, A.J. and Konings, W.N. (1996) Multidrug resistance in lactococcus lactis: evidence for ATP-dependent drug extrusion from the inner leaflet of the cytoplasmic membrane, EMBO J 15: 4239-4245.
11. Busch, E., Krüger, K., Allegrini, P.R., Kerskens, C.M., Gyngell, M.L., Hoehn-Berlage, M. et al. (1998) Reperfusion after thrombolytic therapy of embolic stroke in the rat: magnetic resonance and biochemical imaging, J Cereb Blood Flow Metab 18: 407-418.
12. Comerford, K.M., Wallace, T.J., Karhausen, J., Louis, N.A., Montalto, M.C. and Colgan, S.P. (2002) Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene, Cancer Res 62: 3387-3394.
13. Cotzias, G.C., Papavasiliou, P.S. and Gellene, R. (1969) Modification of Parkinsonism - chronic treatment with L-dopa, N Engl J Med 280: 337-345.
14. Davis, S.M., Lees, K.R., Albers, G.W., Diener, H.C., Markabi, S., Karlsson, G. and Norris, J. (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31: 347-354.
15. Dénes, A., Ferenczi, S., Halász, J., Környei, Z. and Kovács, K.J. (2008) Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse, J Cereb Blood Flow Metab Jun 25.
16. Dimitrijevic, O.B., Stamatovic, S.M., Keep, R.F. and Andjelkovic, A.V. (2007) Absence of the chemokine receptor CCR 2 protects against cerebral ischemia / reperfusion injury in mice, Stroke 38: 1345-1353.
17. Donnan, G.A. (2008) The 2007 Feinberg Lecture: a new road map for neuroprotection, Stroke 39: 242.
18. Endres, M., Namura, S., Shimizu-Sasamata, M., Waeber, C., Zhang, L., Gómez-Isla, T. et al. (1998) Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family, J Cereb Blood Flow Metab 18: 238-247.
19. Felix, R.A. and Barrand, M.A. (2002) P-glycoprotein expression in rat brain endothelial cells: evidence for regulation by transient oxidative stress, J Neurochem 80: 64-72.
20. Fellay, J., Marzolini, C., Meaden, E.R., Back, D.J., Buclin, T., Chave, J.P. et al. (2002) Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study, Lancet 359: 30-36.
21. Festoff, B.W., Suo, Z. and Citron, B.A. (2003) Prospects for the pharmacotherapy of amyotrophic lateral sclerosis: old strategies and new paradigms for the third millennium, CNS Drugs 17: 699-717.
22. Feuerstein, G.Z., Zaleska, M.M., Krams, M., Wang, X., Day, M., Rutkowski, J.L. et al. (2008) Missing steps in the STAIR case: a Translational Medicine perspective on the development of NXY-059 for treatment of acute ischemic stroke, J Cereb Blood Flow Metab 28: 217-219.
23. Garrigues, A., Nugier, J., Orlowski, S. and Ezan, E. (2002) A high-throughput screening microplate test for the interaction of drugs with P-glycoprotein, Anal Biochem 305: 106-114.
24. Gennuso, F., Fernetti, C., Tirolo, C., Testa, N., L'Episcopo, F., Caniglia, S. et al. (2004) Bilirubin protects astrocytes from its own toxicity by inducing up-regulation and translocation of multidrug resistance-associated protein 1 (Mrp1), Proc Natl Acad Sci USA 101: 2470-2475.
25. Gerrard, G., Payne, E., Baker, R.J., Jones, D.T., Potter, M., Prentice, H.G. et al. (2004) Clinical effects and p-glycoprotein inhibition in patients with acute myeloid leukemia treated with zosuquidar trihydrochloride, daunorubicin and cytarabine, Haematologica 89: 782-790.
26. Gottesman, M.M., Fojo, T. and Bates, S.E. (2002) Multidrug resistance in cancer: role of ATP-dependent transporters, Nat Rev Cancer 2: 48-58.
27. Hacke, W., Donnan, G., Fieschi, C., Kaste, M., von Kummer, R., Broderick, J.P. et al. (2004) Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials, Lancet 363: 768-774.
28. Hagenbuch, B. and Meier, P.J. (2004) Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP / SLCO superfamily, new nomenclature and molecular / functional properties, Pflugers Arch 447: 653-665.
29. Hata, R., Maeda, K., Hermann, D., Mies, G. and Hossmann, K.A. (2000 a) Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice, J Cereb Blood Flow Metab 20: 306-315.
30. Hata, R., Maeda, K., Hermann, D., Mies, G. and Hossmann, K.A. (2000 b) Evolution of brain infarction after transient focal cerebral ischemia in mice, J Cereb Blood Flow Metab 20: 937-946.
31. Hermann, D.M., Kilic, E., Hata, R., Hossmann, K.A. and Mies, G. (2001) Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice. Neuroscience 104: 947-955.
32. Hermann, D.M. (2007) Biodistribution processes as underestimated confounders in translational stroke research, Curr Med Chem 14: 3179-3184.
33. Hermann, D.M. and Bassetti, C.L. (2007 a) Implications of ATP-binding cassette transporters for brain pharmacotherapies, Trends Pharmacol Sci 28: 128-134.
34. Hermann, D.M. and Bassetti, C.L. (2007 b) Neuroprotection in the SAINT-II aftermath, Ann Neurol 62: 677-678.
35. Hermann, D.M., Kilic, E., Hata, R., Hossmann, K.A. and Mies, G. (2001) Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice, Neuroscience 104: 947-955.
36. Hermann, D.M., Kilic, E., Spudich, A., Krämer, S.D., Wunderli-Allenspach, H. and Bassetti, C.L. (2006) Role of drug efflux carriers in the healthy and diseased brain, Ann Neurol 60: 489-498.
37. Higgins, C.F. and Linton, K.J. (2004) The ATP switch model for ABC transporters, Nat Struct Mol Biol 11: 918-926.
38. Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H.P., Brockmoller, J., Johne, A. et al. (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo, Proc Natl Acad Sci USA 97: 3473-3478.
39. Hossmann, K.A. (1994) Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised, Brain Pathol 4: 23-36.
40. Hossmann, K.A. (2006) Pathophysiology and therapy of experimental stroke, Cell Mol Neurobiol 26: 1057-1083.
41. Kemper, E.M., van Zandbergen, A.E., Cleypool, C., Mos, H.A., Boogerd, W., Beijnen, J.H. et al. (2003) Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein, Clin Cancer Res 9: 2849-2855.
42. Kieburtz, K. and Ravina, B. (2007) Why hasn't neuroprotection worked in Parkinson's disease? Nat Clin Pract Neurol 3: 240-241.
43. Kilic, E., Hermann, D.M. and Hossmann, K.A. (1998) A reproducible model of thromboembolic stroke in mice, Neuroreport 9: 2967-2970.
44. Kilic, E., Hermann, D.M. and Hossmann, K.A. (2000) Recombinant tissue-plasminogen activator-induced thrombolysis after cerebral thromboembolism in mice, Acta Neuropathol 99: 219-222.
45. Kilic, U., Kilic, E., Reiter, R.J., Bassetti, C.L. and Hermann, D.M. (2005) Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice, J Pineal Res 38: 67-71.
46. Kilic, Ü., Kilic, E., Järve, A., Guo, Z., Spudich, A., Bieber, K. et al. (2006 a) Human vascular endothelial growth factor protects axotomized retinal ganglion cells in vivo by activating ERK-1/2 and Akt pathways, J Neurosci 26: 12439-12446.
47. Kilic, E., Kilic, Ü., Wang, Y., Bassetti, C.L., Marti, H.H. and Hermann, D.M. (2006 b) The phosphatidylinositol-3 kinase / Akt pathway mediates VEGF's neuroprotective activity and induces blood brain barrier permeability after focal cerebral ischemia, FASEB J 20: 1185-1187.
48. Kilic, Ü., Kilic, E., Matter, C.M., Bassetti, C.L. and Hermann, D.M. (2008 a) TLR-4 deficiency protects against focal cerebral ischemia and axotomy-induced neurodegeneration, Neurobiol Dis 31: 33-40.
49. Kilic, E., Kilic, Ü., Bacigaluppi, M., Guo, Z., Abdallah, N.B., Wolfer, D.P., et al. (2008 b) Delayed melatonin administration promotes neuronal survival, neurogenesis and motor recovery, and attenuates hyperactivity and anxiety after mild focal cerebral ischemia in mice, J Pineal Res 45: 142-148.
50. Kornbluth, S. and White, K. (2005) Apoptosis in Drosophila: neither fish nor fowl (nor man, nor worm), J Cell Sci 118: 1779-1787.
51. Kuppens, I.E., Breedveld, P., Beijnen, J.H. and Schellens, J.H. (2005) Modulation of oral drug bioavailability: from preclinical mechanism to therapeutic application, Cancer Invest 23: 443-464.
52. Kusuhara, H. and Sugiyama, Y. (2005) Active efflux across the blood-brain barrier: role of the solute carrier family, NeuroRx 2: 73-85.
53. Lee, Y.J., Maeda, J., Kusuhara, H., Okauchi, T., Inaji, M., Nagai, Y. et al. (2006) In vivo evaluation of P-glycoprotein function at the blood-brain barrier in nonhuman primates using [11C]verapamil, J Pharmacol Exp Ther 316: 647-653.
54. Linker, R.A., Weller, C., Lühder, F., Mohr, A., Schmidt, J., Knauth, M. et al. (2008) Liposomal glucocorticosteroids in treatment of chronic autoimmune demyelination: long-term protective effects and enhanced efficacy of methylprednisolone formulations, Exp Neurol 211: 397-406.
55. Livingston, S., Villamater, C., Sakata, Y. and Pauli, L.L. (1967) Use of carbamazepine in epilepsy. Results in 87 patients, JAMA 200: 204-208.
56. Longa, E.Z., Weinstein, P.R., Carlson, S. and Cummins, R. (1989) Reversible middle cerebral artery occlusion without craniectomy in rats, Stroke 20: 84-91.
57. Löscher, W. and Potschka, H. (2005) Drug resistance in brain diseases and the role of drug efflux transporters, Nat Rev Neurosci 6: 591-602.
58. Martino, G. and Pluchino, S. (2006) The therapeutic potential of neural stem cells, Nat Rev Neurosci 7: 395-406.
59. Marzolini, C., Paus, E., Buclin, T. and Kim, R.B. (2004) Polymorphisms in human MDR 1 (P-glycoprotein): recent advances and clinical relevance, Clin Pharmacol Ther 75: 13-33.
60. Mies, G., Kohno, K. and Hossmann, K.A. (1993) MK-801, a glutamate antagonist, lowers flow threshold for inhibition of protein synthesis after middle cerebral artery occlusion of rat, Neurosci Lett 155: 65-68.
61. Mies, G., Kohno, K. and Hossmann, K.A. (1994) Prevention of periinfarct direct current shifts with glutamate antagonist NBQX following occlusion of the middle cerebral artery in the rat, J Cereb Blood Flow Metab 14: 802-807.
62. MR Stroke Collaborative Group Phan, T.G., Donnan, G.A., Davis, S.M. and Byrnes, G. (2006) Proof-of-principle phase II MRI studies in stroke: sample size estimates from dichotomous and continuous data, Stroke 37: 2521-2525.
63. Murakami, Y., Takamatsu, H., Noda, A., Osoda, K., Ichise, R., Tatsumi, M. et al. (2004) Pharmacokinetic animal PET study of FK 506 as a potent neuroprotective agent, J Nucl Med 45: 1946-1949.
64. Nasi, M., Borghi, V., Pinti, M., Bellodi, C., Lugli, E., Maffei, S. et al. (2003) MDR 1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients. AIDS 17: 1696-1698.
65. NINDS Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 333: 1581-1587.
66. O'Collins, V.E., Macleod, M.R., Donnan, G.A., Horky, L.L., van der Worp, B.H. and Howells, D.W. (2006) 1,026 experimental treatments in acute stroke. Ann Neurol 59: 467-477.
67. Petcu, E.B., Sfredel, V., Platt, D., Herndon, J.G., Kessler, C. and Popa-Wagner, A. (2008) Cellular and molecular events underlying the dysregulated response of the aged brain to stroke: a mini-review, Gerontology 54: 6-17.
68. Polman, C.H., O'Connor, P.W., Havrdova, E., Hutchinson, M., Kappos, L., Miller, D.H. et al. (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis, N Engl J Med 354: 899-910.
69. Rubin, E.H., de Alwis, D.P., Pouliquen, I., Green, L., Marder, P., Lin, Y. et al. (2002) A phase I trial of a potent p-glycoprotein inhibitor, zosuquidar.3HCl trihydrochloride (LY335979), administered orally in combination with doxorubicin in patients with advanced malignancies, Clin Cancer Res 8: 3710-3717.
70. Rudick, R.A., Stuart, W.H., Calabresi, P.A., Confavreux, C., Galetta, S.L., Radue, E.W. et al. (2006) Natalizumab plus interferon beta-1a for relapsing multiple sclerosis, N Engl J Med 354: 911-923.
71. Sauter, A. and Rudin, M. (1995) Strain-dependent drug effects in rat middle cerebral artery occlusion model of stroke, J Pharmacol Exp Ther 274: 1008-1013.
72. Savitz, S.I. and Fisher, M. (2007) Future of neuroprotection for acute stroke: in the aftermath of the SAINT trials, Ann Neurol 61: 396-402.
73. Savitz, S.I. (2007) A critical appraisal of the NXY-059 neuroprotection studies for acute stroke: a need for more rigorous testing of neuroprotective agents in animal models of stroke, Exp Neurol 205: 20-25.
74. Segura, T., Calleja, S. and Jordan, J. (2008) Recommendations and treatment strategies for the management of acute ischemic stroke, Expert Opin Pharmacother 9: 1071-1085.
75. Sehara, Y., Hayashi, T., Deguchi, K., Zhang, H., Tsuchiya, A., Yamashita, T. et al. (2007) Decreased focal inflammatory response by G-CSF may improve stroke outcome after transient middle cerebral artery occlusion in rats, J Neurosci Res 85: 2167-2174.
76. Sharom, F.J. (2006) Shedding light on drug transport: structure and function of the p-glycoprotein multidrug transporter (ABCB1), Biochem Cell Biol 84: 979-992.
77. Shuaib, A., Lees, K.R., Lyden, P., Grotta, J., Davalos, A., Davis, S.M. et al. (2007) NXY-059 for the treatment of acute ischemic stroke, N Engl J Med 357: 562-571.
78. Sharma, V., Prior, J.L., Belinsky, M.G., Kruh, G.D. and Piwnica-Worms, D. (2005) Characterization of a 67Ga/68Ga radiopharmaceutical for SPECT and PET of MDR 1 P-glycoprotein transport activity in vivo: validation in multidrug-resistant tumors and at the blood-brain barrier, J Nucl Med 46: 354-364.
79. Siddiqui, A., Kerb, R., Weale, M.E., Brinkmann, U., Smith, A., Goldstein, D.B. 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.
80. Soontornmalai, A., Vlaming, M.L. and Fritschy, J.M. (2006) Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier, Neuroscience 138: 159-169.
81. Spudich, A., Kilic, E., Xing, H., Kilic, U., Rentsch, K.M., Wunderli-Allenspach et al. ( 2006) Inhibition of multidrug resistance transporter-1 facilitates neuroprotective therapies after focal cerebral ischemia, Nat Neurosci 9: 487-488.
82. Stroke Therapy Academic Industry Roundtable (1999) Recommendations for standards regarding preclinical neuroprotective and restorative drug development, Stroke 30: 2752-2758.
83. Stroke Therapy Academic Industry Roundtable (2001) Recommendations for clinical trial evaluation of acute stroke therapies, Stroke 32: 1598-1606.
84. Stroke Therapy Academic Industry Roundtable (2005) Enhancing the development and approval of acute stroke therapies, Stroke 36: 1808-1813.
85. Thomas, H. and Coley, H.M. (2003) Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein, Cancer Control 10: 159-165.
86. Tidefelt, U., Liliemark, J., Gruber, A., Liliemark, E., Sundman-Engberg, B., Juliusson, G. et al. (2000) P-Glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of daunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia, J Clin Oncol 18: 1837-1844.
87. Villmann, C. and Becker, C.M. (2007) On the hypes and falls in neuroprotection: targeting the NMDA receptor, Neuroscientist 13: 594-615.
88. Wahlgren, N.G. and Ahmed, N. (2004) Neuroprotection in cerebral ischaemia: facts and fancies - the need for new approaches, Cerebrovasc Dis 17(Suppl. 1): 153-166.
89. Wang, Y., Kilic, E., Kilic, U., Weber, B., Bassetti, C.L., Marti, H.H. and Hermann, D.M. (2005) VEGF overexpression induces post-ischaemic neuroprotection, but facilitates haemodynamic steal phenomena, Brain 128: 52-63.
90. Wartenberg, M., Ling, F.C., Muschen, M., Klein, F., Acker, H., Gassmann, M. et al. (2003) Regulation of the multidrug resistance transporter p-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species, FASEB J 17: 503-505.
91. Wenning, G.K., Colosimo, C., Geser, F. and Poewe, W. (2004) Multiple system atrophy, Lancet Neurol 3: 93-103.
92. Yan, N. and Shi, Y. (2005) Mechanisms of apoptosis through structural biology, Annu Rev Cell Dev Biol 21: 35-56.
93. Zhang, Z. and Chopp, M. (2002) Vascular endothelial growth factor and angiopoietins in focal cerebral ischemia, Trends Cardiovasc Med 12: 62-66.
94. Zhang, Z.G., Zhang, L., Ding, G., Jiang, Q., Zhang, R.L., Zhang, X. et al. (2005) A model of mini-embolic stroke offers measurements of the neurovascular unit response in the living mouse, Stroke 36: 2701-2704.
95. Zhang, Z.G., Zhang, L., Jiang, Q., Zhang, R., Davies, K., Powers, C. et al. (2000) VEGF enhances angiogenesis and promotes blood-brain barrier leakage in the ischemic brain, J Clin Invest 106: 829-838.
96. Zhu, H.J. and Liu, G.Q. (2004) Glutamate up-regulates p-glycoprotein expression in rat brain microvessel endothelial cells by an NMDA receptor-mediated mechanism, Life Sci 75: 1313-1322.