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P-glycoprotein and its Role in Treatment Resistance

Year 2016, Volume: 8 Issue: 1, 19 - 31, 23.01.2016

Abstract

Polypharmacy which has often used to increase efficacy of treatment and to prevent resistance in psychiatry may lead to pharmacokinetic and pharmacodynamic drug interactions. One of the intensively studied topic in recent years to clarify the mechanism of drug interactions, in the pharmacokinetic area is p-glycoprotein related drug-drug and drug-food interactions. The interactions of some drugs with p-glycoprotein which is a carrier protein, can lead to a decrease in the bioavailability of these drugs and reduction in passage through the blood-brain barrier. In this review, the role of p-glycoprotein on drug pharmacokinetics and bioavailability of psychiatric drugs are discussed.

References

  • Aszalos A (2007) Drug-drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1) II. Clinical aspects. Drug Discov Today, 12:838-843.
  • Balayssac, D., Authier, N., Cayre A., Coudore, F (2005) Does inhibition of P-glycoprotein lead to drug-drug interactions? Toxicol Lett, 156:319-329.
  • Bartels AL, de Klerk OL, Kortekaas R, de Vries JJ, Leenders KL (2010) 11C-verapamil to assess P-gp function in human brain during aging, depression and neurodegenerative disease. Curr Top Med Chem, 10:1775-1784.
  • 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.
  • Dean, M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res, 11(7):1156-1166.
  • De Klerk OL, Bosker FJ, Luurtsema G, Nolte IM, Dierckx RA, Den Boer JA et al. (2011) The role of P-glycoprotein in psychiatric disorders: a trustful guard of the brain? Cent Nerv Syst Agents Med Chem, 11:197-209.
  • De Klerk OL, Willemsen AT, Bosker FJ, Bartels AL, Hendrikse NH, den Boer JA et al. (2010) Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia: a PET study with [(11)C]verapamil as a probe for P- glycoprotein function. Psychiatry Res, 183:151-156.
  • De Klerk OL, Willemsen AT, Roosink M, Bartels AL, Hendrikse NH, Bosker FJ et al. (2009) Locally increased P-glycoprotein function in major depression: a PET study with [11C]verapamil as a probe for P-glycoprotein function in the blood-brain barrier. Int J Neuropsychopharmacol, 12:895-904.
  • De Luca V, Mındo E, Trakalo J, Wong GW, Kennedy JL (2003) Investigation of polymorphism in the MDR1 gene and antidepressant-inducced mania. Pharmacogenomics J, 3:297-299.
  • Doze P, Van Waarde A, Elsinga PH, Hendrikse NH, Vaalburg W (2000) Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier. Synapse, 36:66-74.
  • Fedoruk MN, Gimenez-Bonafe P, Guns ES, Mayer LD, Nelson CC (2004) P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. Prostate, 59:77-90.
  • Fromm MF (2000) P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int J Clin Pharmacol Ther, 38:69-74.
  • Fromm MF (2002) The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv Drug Deliv Rev, 54:1295-1310.
  • Fromm MF (2004) Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci, 25:423-429.
  • Giessmann T, May K, Modess C, Wegner D, Hecker U, Zschiesche M et al. (2004) Carbamazepine regulates intestinal P- glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther, 76:192-200.
  • Gomez-Gonzalez B, Escobar A (2009) Altered functional development of the blood-brain barrier after early life stress in the rat. Brain Res Bull, 79:376-387.
  • Hadithy AF, Wilffert B, Bruggeman R, Brouwers JR (2008) The impact of MDR1 polymorphisms on prolactin concentrations in patients treated with risperidone. Prog Neuropsychopharmacol Biol Psychiatry, 32:593-594.
  • Huls M, Russel FG, Masereeuw R (2009) The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther, 328:3-9.
  • Johnstone RW, Ruefli AA, Smyth MJ (2000) Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem Sci, 25:1-6.
  • Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta, 455:152-162.
  • Kara ZP, Öztürk N, Öztürk D, Okyar A (2013) ABC taşıyıcı proteinleri: sirkadiyan ritimler ve cinsiyete bağlı farklılıklar. Marmara Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 3:1-13.
  • Kelsey JE (2006) Basics of psychopharmacology. In Principles of Psychopharmacology for Mental Health Professionals (Eds JE Kelsey, DJ Newport, CB Nemeroff):9-37. New Jersey, Wiley.
  • Kioka N, Tsubota J, Kakehi Y, Komano T, Gottesman MM, Pastan I et al. (1989) P-glycoprotein carriers Gly 185 with an altered pattern of multidrug resistance. Biochem Biophsy Res Commun, 162:285-307.
  • Laika B, Leucht S, Steimer W (2006) ABCB1 (P-glycoprotein/MDR1) gene G2677T/a sequence variation (polymorphism): lack of association with side effects and therapeutic response in depressed inpatients treated with amitriptyline. Clin Chem, 52:893- 895.
  • Lin, JH, Yamazaki M (2003) Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet, 42:59-98.
  • Linnet K, Ejsing TB (2008) A review on the impact of P-glycoprotein on the penetration of drugs into the brain: focus on psychotropic drugs. Eur Neuropsychopharmacol, 18:157-169.
  • Malhotra AK, Murphy GM. Jr, Kennedy JL (2004) Pharmacogenetics of psychotropic drug response. Am J Psychiatry, 161:780-796.
  • Marchetti S. Mazzanti R. Beijnen JH, Schellens JH (2007) Concise review: Clinical relevance of drug-drug and herb-drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist, 12:927-941.
  • Marzolini C, Paus E, Buclin T, Kim RB (2004) Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther, 75:13-33.
  • Menu P, Gressier F, Verstuyft C, Hardy P, Becquemont L, Corruble E (2010) Antidepressants and ABCB1 gene C3435T functional polymorphism: a naturalistic study. Neuropsychobiology, 62:193-197.
  • Mihaljevic Peles A, Bozina N, Sagud M, Rojnic Kuzman M, Lovric M (2008) MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry, 32:1439-1444.
  • Morjani H, Madoulet C (2010) Immunosuppressors as multidrug resistance reversal agents. Meth Mol Biol, 596:433-446.
  • O'Brien FE, Clarke G, Fitzgerald P, Dinan TG, Griffin BT, Cryan JF (2012) Inhibition of P-glycoprotein enhances transport of imipramine across the blood-brain barrier: microdialysis studies in conscious freely moving rats. Br J Pharmacol, 166:1333- 1343.
  • O'Brien FE, O'Connor RM, Clarke G, Dinan TG, Griffin BT, Cryan JF (2013) P-glycoprotein inhibition increases the brain distribution and antidepressant-like activity of escitalopram in rodents. Neuropsychopharmacology, 38:2209–2219.
  • Padowski JM, Pollack GM (2010) Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation. Methods Mol Biol, 596:359-384.
  • Potschka H (2010) Targeting regulation of ABC efflux transporters in brain diseases:a novel therapeutic approach. Pharmacol Ther, 125:118-127.
  • Ramakrishnan P (2003) The role of P-glycoprotein in the blood-brain barrier. Einstein Q J Biol Med, 19:160-165.
  • Rees DC, Johnson E, Lewinson, O (2009) ABC transporters: the power to change. Nat Rev Mol Cell Biol, 10:218-227.
  • Seelig A, Gatlik-Landwojtowicz E (2005) Inhibitors of multidrug efflux transporters: their membrane and protein interactions. Mini Rev Med Chem, 5:135-151.
  • Schinkel AH (1997) The physiological function of drug-transporting P-glycoproteins. Semin Cancer Biol, 8:161-170.
  • Schinkel AH (1999) P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev, 36:179-194.
  • Schwab M, Eichelbaum M, Fromm MF (2003) Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev Pharmacol Toxicol, 43:285-307.
  • Sinton CM, Fitch TE, Petty F, Haley RW (2000) Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the rat. Toxicol Appl Pharmacol, 165:99-105.
  • Spahn-Langguth H, Baktır G, Radschuweit A, Okyar A, Terhaag B, Ader P et al. (1998) P-glycoprotein transporters and the gastrointestinal tract: evaluation of the potential in vivo relevance of in vitro data employing talinolol as model compound. Int J Clin Pharmacol Ther, 36:16-24.
  • Spector R (2000) Drug Transport in the mammalian central nervous system: multiple complex systems . a critical analysis and commentary. Pharmacology, 60:58-73.
  • Stavrovskaya AA, Stromskaya TP (2008) Transport proteins of the ABC family and multidrug resistance of tumor cells. Biochemistry (Mosc), 73:592-604.
  • Suzuki T, Zhao YL, Nadai M, Naruhashi K, Shimizu A, Takagi K et al. (2006) Gender-related differences in expression and function of hepatic P-glycoprotein and multidrug resistance-associated protein (Mrp2) in rats. Life Sci, 79:455-461.
  • Suzuki Y, Tsuneyama N, Fukui N, Sugai T, Watanabe J, Ono S et al. (2014) Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia. Pharmacogenomics J, 14452-456.
  • Takano M, Yumoto R, Murakami T (2006) Expression and function of efflux drug transporters in the intestine. Pharmacol Ther, 109:137-161.
  • Thoeringer CK, Wultsch T, Shahbazian A, Painsipp E, Holzer P (2009) Multidrug-resistance gene 1-type p-glycoprotein (MDR1 p- gp) inhibition by tariquidar impacts on neuroendocrine and behavioral processing of stress. Psychoneuroendocrinology, 32:1028-1040.
  • Toornvliet R, van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM et al. (2006) Effect of age on functional P- glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography. Clin Pharmacol Ther, 79:540-548.
  • Urquhart BL, Kim RB (2009) Blood-brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol, 65:1063- 1070.
  • Wang JS, Zhu HJ, Donovan JL, Yuan HJ, Markowitz JS, Geesey ME et al. (2009) Aripiprazole brain concentration is altered in P- glycoprotein deficient mice. Schizophr Res, 110:90-94.
  • Xie Y, Liu J, Liu Y, Klaassen CD, Waalkes MP (2004) Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug- resistance mdr1a/1b(-/-) double knockout mice. Mol Cell Biochem, 255:11-18.
  • Yasui-Farukori N, SaitoM, Nakagami T, Kaneda A, Tateishi T, Kaneko S (2006) Association between multidrug resistance-1 (MDR1) gene polymorphisms and therapeutic response to bromperidol in schizophrenic patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry, 30:286-291.
  • Zhou SF (2008) Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica, 38:802-832.
  • Işıl Göğcegöz Gül, Yrd.Doç.Dr., Üsküdar Üniversitesi, İstanbul; Gül Eryılmaz, Yrd.Doç.Dr., Üsküdar Üniversi
  • tesi, İstanbul; K. Oğuz Karamustafalıoğlu, Prof.Dr., Üsküdar Üniversitesi, İstanbul

P-glikoprotein ve Tedaviye Dirençteki Rolü

Year 2016, Volume: 8 Issue: 1, 19 - 31, 23.01.2016

Abstract

Psikiyatride tedavi etkinliğini artırmak ve direnci önlemek amacıyla sıklıkla uygulanan polifarmasi, farmakokinetik ve farmakodinamik ilaç etkileşimlerine neden olabilmektedir. İlaç etkileşim mekanizmalarının aydınlatılması amacıyla, farmakokinetik alanında son yıllarda üzerinde yoğun olarak çalışılan bir konu p-glikoproteine bağlı ilaç-ilaç ve ilaç-besin etkileşmeleridir. Bazı ilaçların bir taşıyıcı protein olan p-glikoprotein ile olan etkileşmeleri, bu ilaçların biyoyararlanımlarında düşüşe ve kan-beyin bariyerinden geçişlerinde azalmaya yol açabilmektedir. Bu derlemede, p-glikoproteinin ilaç farmakokinetiğinde ve psikiyatrik ilaçların biyoyararlanımındaki rolü tartışılmıştır.

References

  • Aszalos A (2007) Drug-drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1) II. Clinical aspects. Drug Discov Today, 12:838-843.
  • Balayssac, D., Authier, N., Cayre A., Coudore, F (2005) Does inhibition of P-glycoprotein lead to drug-drug interactions? Toxicol Lett, 156:319-329.
  • Bartels AL, de Klerk OL, Kortekaas R, de Vries JJ, Leenders KL (2010) 11C-verapamil to assess P-gp function in human brain during aging, depression and neurodegenerative disease. Curr Top Med Chem, 10:1775-1784.
  • 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.
  • Dean, M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res, 11(7):1156-1166.
  • De Klerk OL, Bosker FJ, Luurtsema G, Nolte IM, Dierckx RA, Den Boer JA et al. (2011) The role of P-glycoprotein in psychiatric disorders: a trustful guard of the brain? Cent Nerv Syst Agents Med Chem, 11:197-209.
  • De Klerk OL, Willemsen AT, Bosker FJ, Bartels AL, Hendrikse NH, den Boer JA et al. (2010) Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia: a PET study with [(11)C]verapamil as a probe for P- glycoprotein function. Psychiatry Res, 183:151-156.
  • De Klerk OL, Willemsen AT, Roosink M, Bartels AL, Hendrikse NH, Bosker FJ et al. (2009) Locally increased P-glycoprotein function in major depression: a PET study with [11C]verapamil as a probe for P-glycoprotein function in the blood-brain barrier. Int J Neuropsychopharmacol, 12:895-904.
  • De Luca V, Mındo E, Trakalo J, Wong GW, Kennedy JL (2003) Investigation of polymorphism in the MDR1 gene and antidepressant-inducced mania. Pharmacogenomics J, 3:297-299.
  • Doze P, Van Waarde A, Elsinga PH, Hendrikse NH, Vaalburg W (2000) Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier. Synapse, 36:66-74.
  • Fedoruk MN, Gimenez-Bonafe P, Guns ES, Mayer LD, Nelson CC (2004) P-glycoprotein increases the efflux of the androgen dihydrotestosterone and reduces androgen responsive gene activity in prostate tumor cells. Prostate, 59:77-90.
  • Fromm MF (2000) P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int J Clin Pharmacol Ther, 38:69-74.
  • Fromm MF (2002) The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv Drug Deliv Rev, 54:1295-1310.
  • Fromm MF (2004) Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol Sci, 25:423-429.
  • Giessmann T, May K, Modess C, Wegner D, Hecker U, Zschiesche M et al. (2004) Carbamazepine regulates intestinal P- glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin Pharmacol Ther, 76:192-200.
  • Gomez-Gonzalez B, Escobar A (2009) Altered functional development of the blood-brain barrier after early life stress in the rat. Brain Res Bull, 79:376-387.
  • Hadithy AF, Wilffert B, Bruggeman R, Brouwers JR (2008) The impact of MDR1 polymorphisms on prolactin concentrations in patients treated with risperidone. Prog Neuropsychopharmacol Biol Psychiatry, 32:593-594.
  • Huls M, Russel FG, Masereeuw R (2009) The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther, 328:3-9.
  • Johnstone RW, Ruefli AA, Smyth MJ (2000) Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem Sci, 25:1-6.
  • Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta, 455:152-162.
  • Kara ZP, Öztürk N, Öztürk D, Okyar A (2013) ABC taşıyıcı proteinleri: sirkadiyan ritimler ve cinsiyete bağlı farklılıklar. Marmara Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 3:1-13.
  • Kelsey JE (2006) Basics of psychopharmacology. In Principles of Psychopharmacology for Mental Health Professionals (Eds JE Kelsey, DJ Newport, CB Nemeroff):9-37. New Jersey, Wiley.
  • Kioka N, Tsubota J, Kakehi Y, Komano T, Gottesman MM, Pastan I et al. (1989) P-glycoprotein carriers Gly 185 with an altered pattern of multidrug resistance. Biochem Biophsy Res Commun, 162:285-307.
  • Laika B, Leucht S, Steimer W (2006) ABCB1 (P-glycoprotein/MDR1) gene G2677T/a sequence variation (polymorphism): lack of association with side effects and therapeutic response in depressed inpatients treated with amitriptyline. Clin Chem, 52:893- 895.
  • Lin, JH, Yamazaki M (2003) Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet, 42:59-98.
  • Linnet K, Ejsing TB (2008) A review on the impact of P-glycoprotein on the penetration of drugs into the brain: focus on psychotropic drugs. Eur Neuropsychopharmacol, 18:157-169.
  • Malhotra AK, Murphy GM. Jr, Kennedy JL (2004) Pharmacogenetics of psychotropic drug response. Am J Psychiatry, 161:780-796.
  • Marchetti S. Mazzanti R. Beijnen JH, Schellens JH (2007) Concise review: Clinical relevance of drug-drug and herb-drug interactions mediated by the ABC transporter ABCB1 (MDR1, P-glycoprotein). Oncologist, 12:927-941.
  • Marzolini C, Paus E, Buclin T, Kim RB (2004) Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther, 75:13-33.
  • Menu P, Gressier F, Verstuyft C, Hardy P, Becquemont L, Corruble E (2010) Antidepressants and ABCB1 gene C3435T functional polymorphism: a naturalistic study. Neuropsychobiology, 62:193-197.
  • Mihaljevic Peles A, Bozina N, Sagud M, Rojnic Kuzman M, Lovric M (2008) MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry, 32:1439-1444.
  • Morjani H, Madoulet C (2010) Immunosuppressors as multidrug resistance reversal agents. Meth Mol Biol, 596:433-446.
  • O'Brien FE, Clarke G, Fitzgerald P, Dinan TG, Griffin BT, Cryan JF (2012) Inhibition of P-glycoprotein enhances transport of imipramine across the blood-brain barrier: microdialysis studies in conscious freely moving rats. Br J Pharmacol, 166:1333- 1343.
  • O'Brien FE, O'Connor RM, Clarke G, Dinan TG, Griffin BT, Cryan JF (2013) P-glycoprotein inhibition increases the brain distribution and antidepressant-like activity of escitalopram in rodents. Neuropsychopharmacology, 38:2209–2219.
  • Padowski JM, Pollack GM (2010) Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation. Methods Mol Biol, 596:359-384.
  • Potschka H (2010) Targeting regulation of ABC efflux transporters in brain diseases:a novel therapeutic approach. Pharmacol Ther, 125:118-127.
  • Ramakrishnan P (2003) The role of P-glycoprotein in the blood-brain barrier. Einstein Q J Biol Med, 19:160-165.
  • Rees DC, Johnson E, Lewinson, O (2009) ABC transporters: the power to change. Nat Rev Mol Cell Biol, 10:218-227.
  • Seelig A, Gatlik-Landwojtowicz E (2005) Inhibitors of multidrug efflux transporters: their membrane and protein interactions. Mini Rev Med Chem, 5:135-151.
  • Schinkel AH (1997) The physiological function of drug-transporting P-glycoproteins. Semin Cancer Biol, 8:161-170.
  • Schinkel AH (1999) P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Deliv Rev, 36:179-194.
  • Schwab M, Eichelbaum M, Fromm MF (2003) Genetic polymorphisms of the human MDR1 drug transporter. Annu Rev Pharmacol Toxicol, 43:285-307.
  • Sinton CM, Fitch TE, Petty F, Haley RW (2000) Stressful manipulations that elevate corticosterone reduce blood-brain barrier permeability to pyridostigmine in the rat. Toxicol Appl Pharmacol, 165:99-105.
  • Spahn-Langguth H, Baktır G, Radschuweit A, Okyar A, Terhaag B, Ader P et al. (1998) P-glycoprotein transporters and the gastrointestinal tract: evaluation of the potential in vivo relevance of in vitro data employing talinolol as model compound. Int J Clin Pharmacol Ther, 36:16-24.
  • Spector R (2000) Drug Transport in the mammalian central nervous system: multiple complex systems . a critical analysis and commentary. Pharmacology, 60:58-73.
  • Stavrovskaya AA, Stromskaya TP (2008) Transport proteins of the ABC family and multidrug resistance of tumor cells. Biochemistry (Mosc), 73:592-604.
  • Suzuki T, Zhao YL, Nadai M, Naruhashi K, Shimizu A, Takagi K et al. (2006) Gender-related differences in expression and function of hepatic P-glycoprotein and multidrug resistance-associated protein (Mrp2) in rats. Life Sci, 79:455-461.
  • Suzuki Y, Tsuneyama N, Fukui N, Sugai T, Watanabe J, Ono S et al. (2014) Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia. Pharmacogenomics J, 14452-456.
  • Takano M, Yumoto R, Murakami T (2006) Expression and function of efflux drug transporters in the intestine. Pharmacol Ther, 109:137-161.
  • Thoeringer CK, Wultsch T, Shahbazian A, Painsipp E, Holzer P (2009) Multidrug-resistance gene 1-type p-glycoprotein (MDR1 p- gp) inhibition by tariquidar impacts on neuroendocrine and behavioral processing of stress. Psychoneuroendocrinology, 32:1028-1040.
  • Toornvliet R, van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM et al. (2006) Effect of age on functional P- glycoprotein in the blood-brain barrier measured by use of (R)-[(11)C]verapamil and positron emission tomography. Clin Pharmacol Ther, 79:540-548.
  • Urquhart BL, Kim RB (2009) Blood-brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol, 65:1063- 1070.
  • Wang JS, Zhu HJ, Donovan JL, Yuan HJ, Markowitz JS, Geesey ME et al. (2009) Aripiprazole brain concentration is altered in P- glycoprotein deficient mice. Schizophr Res, 110:90-94.
  • Xie Y, Liu J, Liu Y, Klaassen CD, Waalkes MP (2004) Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug- resistance mdr1a/1b(-/-) double knockout mice. Mol Cell Biochem, 255:11-18.
  • Yasui-Farukori N, SaitoM, Nakagami T, Kaneda A, Tateishi T, Kaneko S (2006) Association between multidrug resistance-1 (MDR1) gene polymorphisms and therapeutic response to bromperidol in schizophrenic patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry, 30:286-291.
  • Zhou SF (2008) Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica, 38:802-832.
  • Işıl Göğcegöz Gül, Yrd.Doç.Dr., Üsküdar Üniversitesi, İstanbul; Gül Eryılmaz, Yrd.Doç.Dr., Üsküdar Üniversi
  • tesi, İstanbul; K. Oğuz Karamustafalıoğlu, Prof.Dr., Üsküdar Üniversitesi, İstanbul
There are 58 citations in total.

Details

Primary Language English
Journal Section Review
Authors

İşıl Göğcegöz Gül This is me

Gül Eryılmaz This is me

K. Oğuz Karamustafalıoğlu This is me

Publication Date January 23, 2016
Published in Issue Year 2016 Volume: 8 Issue: 1

Cite

AMA Göğcegöz Gül İ, Eryılmaz G, Karamustafalıoğlu KO. P-glycoprotein and its Role in Treatment Resistance. Psikiyatride Güncel Yaklaşımlar - Current Approaches in Psychiatry. January 2016;8(1):19-31.

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