Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
December-2018 Volume 16 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2018 Volume 16 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein

  • Authors:
    • Yangang Zhou
    • Huande Li
    • Ping Xu
    • Li Sun
    • Qing Wang
    • Qiong Lu
    • Haiyan Yuan
    • Yiping Liu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China
  • Pages: 5410-5416
    |
    Published online on: October 11, 2018
       https://doi.org/10.3892/etm.2018.6847
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Paliperidone (PAL) is a relatively novel atypical antipsychotic drug for schizophrenia that induces markedly varying responses. Breast cancer resistance protein (BCRP) is a recently discovered member of the ATP‑binding cassette superfamily that has been used to control drug absorption, distribution and elimination, and especially to impede drug entry into the brain. To the best of our knowledge, the present study is the first to investigate the possibility of using PAL as a BCRP substrate. The intracellular accumulation and bidirectional transport were investigated using transfected 293 cell/BCRP and porcine renal endothelial cell (LLC‑PK1)/BCRP cell monolayers and BCRP overexpression was confirmed by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The in vitro affinity to BCRP was assessed in human BCRP (Arg482) membranes. The intracellular accumulation and bidirectional transport investigations demonstrated that BCRP can efflux PAL from cells and significantly decrease its cellular concentration over a concentration range of 0.1‑50 µM. The in vitro affinity experiments indicated that PAL has a moderate affinity to BCRP at 0.1‑100 µM. These results together suggest that PAL is a substrate for BCRP and that it can affect the blood‑brain barrier penetration of PAL at therapeutic dosages.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Tandon R, Belmaker RH, Gattaz WF, Lopez-Ibor JJ Jr, Okasha A, Singh B, Stein DJ and Olie JP: Fleischhacker WW and Moeller HJ; Section of Pharmacopsychiatry, World Psychiatric Association: World Psychiatric Association Pharmacopsychiatry Section statement on comparative effectiveness of antipsychotics in the treatment of schizophrenia. Schizophr Res. 100:20–38. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Chong HY, Teoh SL, Wu DB, Kotirum S, Chiou CF and Chaiyakunapruk N: Global economic burden of schizophrenia: A systematic review. Neuropsychiatr Dis Treat. 12:357–373. 2016.PubMed/NCBI

3 

Samara MT, Dold M, Gianatsi M, Nikolakopoulou A, Helfer B, Salanti G and Leucht S: Efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia: A network meta-analysis. JAMA Psychiatry. 73:199–210. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Owen MJ, Sawa A and Mortensen PB: Schizophrenia. Lancet. 388:86–97. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Suzuki T, Remington G, Mulsant BH, Rajji TK, Uchida H, Graff-Guerrero A and Mamo DC: Treatment resistant schizophrenia and response to antipsychotics: A review. Schizophr Res. 133:54–62. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Chwieduk CM and Keating GM: Paliperidone extended release: A review of its use in the management of schizophrenia. Drugs. 70:1295–1317. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Wang SM, Han C, Lee SJ, Patkar AA, Pae CU and Fleischhacker WW: Paliperidone: A review of clinical trial data and clinical implications. Clin Drug Investig. 32:497–512. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Nussbaum AM and Stroup TS: Paliperidone for treatment of schizophrenia. Schizophr Bull. 34:419–422. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Spina E and Cavallaro R: The pharmacology and safety of paliperidone extended-release in the treatment of schizophrenia. Expert Opin Drug Saf. 6:651–662. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Breedvel P, Benjnen JH and Schellens JH: Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci. 27:17–24. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Ueno M, Nakagawa T, Wu B, Onodera M, Huang CL, Kusaka T, Araki N and Sakamoto H: Transporters in the brain endothelial barrier. Curr Med Chem. 17:1125–1138. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Begley DJ: ABC transporters and the blood-brain barrier. Curr Pharm Des. 10:1295–1312. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Vermeir M, Naessens I, Remmerie B, Mannens G, Hendrickx J, Sterkens P, Talluri K, Boom S, Eerdekens M, van Osselaer N and Cleton A: Absorption, metabolism, and excretion of paliperidone, a new monoaminergic antagonist, in humans. Drug Metab Dispos. 36:769–779. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Suzuki Y, Tsuneyama N, Fukui N, Sugai T, Watanabe J, Ono S, Saito M and Someya T: Impact of the ABCB1 gene polymorphism on plasma 9-hydroxyrisperidone and active moiety levels in Japanese patients with schizophrenia. J Clin Psychopharmacol. 33:411–414. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS and DeVane CL: The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein. Int J Neuropsychopharmacol. 7:415–419. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Jani M, Ambrus C, Magnan R, Jakab KT, Beéry E, Zolnerciks JK and Krajcsi P: Structure and function of BCRP, a broad specificity transporter of xenobiotics and endobiotics. Arch Toxicol. 88:1205–1248. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Wang JS, Zhu HJ, Markowitz JS, Donovan JL, Yuan HJ and Devane CL: Antipsychotic drugs inhibit the function of breast cancer resistance protein. Basic Clin Pharmacol Toxicol. 103:336–341. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Tian Y, Qu BX, Yao Y and Zeng S: Establishment of BCRP expressed pig kidney cell line LLC-PK1/BCRP and its biological profile. Yao Xue Xue Bao. 47:1599–1604. 2012.(In Chinese). PubMed/NCBI

19 

Yan H, Zhang DY, Li X, Yuan XQ, Yang YL, Zhu KW, Zeng H, Li XL, Cao S, Zhou HH, et al: Long non-coding RNA GAS5 polymorphism predicts a poor prognosis of acute myeloid leukemia in Chinese patients via affecting hematopoietic reconstitution. Leuk Lymphoma. 58:1948–1957. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Feng B, Mills JB, Davidson RE, Mireles RJ, Janiszewski JS, Troutman MD and de Morais SM: In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system. Drug Metab Dispos. 36:268–275. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Boulton DW, DeVane CL, Liston HL and Markowitz JS: In vitro P-glycoprotein affinity for atypical and conventional antipsychotics. Life Sci. 71:163–169. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Kim KA, Joo HJ, Lee HM and Park JY: Influence of ABCB1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of quetiapine in healthy volunteers. Pharmacogenet Genomics. 24:35–42. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Hoosain FG, Choonara YE, Tomar LK, Kumar P, Tyagi C, du Toit LC and Pillay V: Bypassing P-glycoprotein drug efflux mechanisms: Possible applications in pharmacoresistant schizophrenia therapy. Biomed Res Int. 2015:4849632015. View Article : Google Scholar : PubMed/NCBI

24 

Tian Y, Qian S, Jiang Y, Shen Q, Zheng J, Zhou H and Zeng S: The interaction between human breast cancer resistance protein (BCRP) and five bisbenzylisoquinoline alkaloids. Int J Pharm. 453:371–379. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Takada T, Suzuki H and Sugiyama Y: Characterization of polarized expression of point- or deletion-mutated human BCRP/ABCG2 in LLC-PK1 cells. Pharm Res. 22:458–464. 2005.Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I and Gottesman MM: Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol. 39:361–398, 1999. View Article : Google Scholar : PubMed/NCBI

26 

Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I and Gottesman MM: Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol. 39:361–98. 1999. View Article : Google Scholar : PubMed/NCBI

27 

Hrycyna CA, Ramachandra M, Ambudkar SV, Ko YH, Pedersen PL, Pastan I and Gottesman MM: Mechanism of action of human P-glycoprotein ATPase activity. Photochemical cleavage during a catalytic transition state using orthovanadate reveals cross-talk between the two ATP sites. J Biol Chem. 273:16631–16634. 1998.

28 

Ozvegy-Laczka C, Köblös G, Sarkadi B and Váradi A: Single amino acid (482) variants of the ABCG2 multidrug transporter: Major differences in transport capacity and substrate recognition. Biochim Biophys Acta. 1668:53–63. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Shukla S, Robey RW, Bates SE and Ambudkar SV: The calcium channel blockers, 1,4-dihydropyridines, are substrates of the multidrug resistance-linked ABC drug transporter, ABCG2. Biochemistry. 45:8940–8951. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Eddabra L, Wenner T, El Btaouri H, Baranek T, Madoulet C, Cornillet-Lefebvre P and Morjani H: Arginine 482 to glycine mutation in ABCG2/BCRP increases etoposide transport and resistance to the drug in HEK-293 cells. Oncol Rep. 27:232–237. 2012.PubMed/NCBI

31 

de Leon J, Wynn G and Sandson NB: The pharmacokinetics of paliperidone versus risperidone. Psychosomatics. 51:80–88. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Lindenmayer JP and Kaur A: Antipsychotic management of schizoaffective disorder: A review. Drugs. 76:589–604. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhou Y, Li H, Xu P, Sun L, Wang Q, Lu Q, Yuan H and Liu Y: Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein. Exp Ther Med 16: 5410-5416, 2018.
APA
Zhou, Y., Li, H., Xu, P., Sun, L., Wang, Q., Lu, Q. ... Liu, Y. (2018). Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein. Experimental and Therapeutic Medicine, 16, 5410-5416. https://doi.org/10.3892/etm.2018.6847
MLA
Zhou, Y., Li, H., Xu, P., Sun, L., Wang, Q., Lu, Q., Yuan, H., Liu, Y."Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein". Experimental and Therapeutic Medicine 16.6 (2018): 5410-5416.
Chicago
Zhou, Y., Li, H., Xu, P., Sun, L., Wang, Q., Lu, Q., Yuan, H., Liu, Y."Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein". Experimental and Therapeutic Medicine 16, no. 6 (2018): 5410-5416. https://doi.org/10.3892/etm.2018.6847
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Y, Li H, Xu P, Sun L, Wang Q, Lu Q, Yuan H and Liu Y: Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein. Exp Ther Med 16: 5410-5416, 2018.
APA
Zhou, Y., Li, H., Xu, P., Sun, L., Wang, Q., Lu, Q. ... Liu, Y. (2018). Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein. Experimental and Therapeutic Medicine, 16, 5410-5416. https://doi.org/10.3892/etm.2018.6847
MLA
Zhou, Y., Li, H., Xu, P., Sun, L., Wang, Q., Lu, Q., Yuan, H., Liu, Y."Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein". Experimental and Therapeutic Medicine 16.6 (2018): 5410-5416.
Chicago
Zhou, Y., Li, H., Xu, P., Sun, L., Wang, Q., Lu, Q., Yuan, H., Liu, Y."Paliperidone, a relatively novel atypical antipsychotic drug, is a substrate for breast cancer resistance protein". Experimental and Therapeutic Medicine 16, no. 6 (2018): 5410-5416. https://doi.org/10.3892/etm.2018.6847
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team