The poorly membrane permeable antipsychotic drugs amisulpride and sulpiride are substrates of the organic cation transporters from the slc22 family

AAPS Journal

Volumn 16, Issue 6, 2014, Pages 1247-1256

  Pereira, Joao N Dos Santos ^a   Tadjerpisheh, Sina ^a   Abed, Manar Abu ^a   Saadatmand, Ali R ^a   Weksler, Babette ^b   Romero, Ignacio A ^c   Couraud, Pierre Olivier ^d,e,f   Brockmöller, Jürgen ^a   Tzvetkov, Mladen V ^a  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c OPEN UNIVERSITY   (United Kingdom)

^d INSTITUT COCHIN   (France)

^e CNRS   (France)

^f UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

Amisulpride; Blood brain barrier; Membrane permeability; Organic cation transporters; Sulpiride

Indexed keywords

AMISULPRIDE; CARNITINE TRANSPORTER 1; CARNITINE TRANSPORTER 2; ORGANIC CATION TRANSPORTER; ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3; SULPIRIDE; SULTOPRIDE; TIAPRIDE; ARTIFICIAL MEMBRANE; NEUROLEPTIC AGENT;

ARTICLE; ARTIFICIAL MEMBRANE; BLOOD BRAIN BARRIER; BRAIN CELL; CAPILLARY ENDOTHELIAL CELL; CONTROLLED STUDY; DRUG DISTRIBUTION; DRUG PENETRATION; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TRANSPORT; DRUG UPTAKE; EMBRYO; HEK293 CELL LINE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; MEMBRANE PERMEABILITY; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN POLYMORPHISM; TANDEM MASS SPECTROMETRY; TRANSPORT KINETICS; ANALOGS AND DERIVATIVES; BIOLOGICAL MODEL; CELL MEMBRANE PERMEABILITY; DRUG EFFECTS; ENDOTHELIUM CELL; ENZYME SPECIFICITY; GENETIC TRANSFECTION; GENETICS; METABOLISM; MICROVASCULATURE; TRANSPORT AT THE CELLULAR LEVEL;

ANTIPSYCHOTIC AGENTS; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; CELL MEMBRANE PERMEABILITY; ENDOTHELIAL CELLS; HEK293 CELLS; HUMANS; MEMBRANES, ARTIFICIAL; MICROVESSELS; MODELS, BIOLOGICAL; ORGANIC CATION TRANSPORT PROTEINS; SUBSTRATE SPECIFICITY; SULPIRIDE; TRANSFECTION;

EID: 84938808704     PISSN: None     EISSN: 15507416     Source Type: Journal    
DOI: 10.1208/s12248-014-9649-9     Document Type: Article

References (54)

1. Strazielle N, Ghersi-Egea JF. Physiology of blood–brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm. 2013;10(5):1473–91.
2. Zamek-Gliszczynski MJ, Hoffmaster KA, Tweedie DJ, Giacomini KM, Hillgren KM. Highlights from the international transporter consortium second workshop. Clin Pharmacol Ther. 2012;92(5):553–6.
3. Benet L, Broccatelli F, Oprea T. BDDCS applied to over 900 drugs. AAPS J. 2011;13(4):519–47.
4. Culot M, Fabulas-da Costa A, Sevin E, Szorath E, Martinsson S, Renftel M, et al. A simple method for assessing free brain/free plasma ratios using an in vitro model of the blood brain barrier. PLoS ONE. 2013;8(12):e80634.
5. Dufour A, De Santi C. Pharmacokinetics and metabolism of amisulpride (In French). Ann Psychiatr. 1988;3:7.
6. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, et al. Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008;51(19):5932–42.
7. Kido Y, Matsson P, Giacomini KM. Profiling of a prescription drug library for potential renal drug–drug interactions mediated by the Organic Cation Transporter 2. J Med Chem. 2011;54(13):4548–58.
8. Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res. 2007;24(7):1227–51.
9. Nies A, Koepsell H, Damme K, Schwab M. Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy. In: Fromm MF, Kim RB, editors. Drug transporters. Handbook of experimental pharmacology. Berlin: 201: Springer; 2011. p. 105–67.
10. Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest. 2007;117(5):1422–31.
11. Tzvetkov MV, dos Santos Pereira JN, Meineke I, Saadatmand AR, Stingl JC, Brockmöller J. Morphine is a substrate of the organic cation transporter OCT1 and polymorphisms in OCT1 gene affect morphine pharmacokinetics after codeine administration. Biochemical Pharmacology. 2013(0).
12. Tzvetkov MV, Saadatmand AR, Bokelmann K, Meineke I, Kaiser R, Brockmoller J. Effects of OCT1 polymorphisms on the cellular uptake, plasma concentrations and efficacy of the 5-HT3 antagonists tropisetron and ondansetron. Pharmacogenomics J. 2012;12(1):22–9.
13. Tzvetkov MV, Saadatmand AR, Lotsch J, Tegeder I, Stingl JC, Brockmoller J. Genetically polymorphic OCT1: another piece in the puzzle of the variable pharmacokinetics and pharmacodynamics of the opioidergic drug tramadol. Clin Pharmacol Ther. 2011;90(1):143–50.
14. Morrissey KM, Stocker SL, Wittwer MB, Xu L, Giacomini KM. Renal transporters in drug development. Annu Rev Pharmacol Toxicol. 2013;53(1):503–29.
15. Lin C-J, Tai Y, Huang M-T, Tsai Y-F, Hsu H-J, Tzen K-Y, et al. Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood–brain barrier and MPTP-induced dopaminergic toxicity in rodents. J Neurochem. 2010;114(3):717–27.
16. Dickens D, Owen A, Alfirevic A, Giannoudis A, Davies A, Weksler B, et al. Lamotrigine is a substrate for OCT1 in brain endothelial cells. Biochem Pharmacol. 2012;83(6):805–14.
17. Grundemann D, Schechinger B, Rappold G, Schomig E. Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998;1(5):349–51.
18. Koepsell H. The SLC22 family with transporters of organic cations, anions and zwitterions. Mol Asp Med. 2013;34(2–3):413–35.
19. Kido Y, Tamai I, Ohnari A, Sai Y, Kagami T, Nezu J-i, et al. Functional relevance of carnitine transporter OCTN2 to brain distribution of l-carnitine and acetyl-l-carnitine across the blood–brain barrier. J Neurochem. 2001;79(5):959–69.
20. Okura T, Kato S, Deguchi Y. Functional expression of organic cation/carnitine transporter 2 (OCTN2/SLC22A5) in human brain capillary endothelial cell line hCMEC/D3, a human blood–brain barrier model. Drug Metab Pharmacokinet. 2014;29(1):5.
21. Saadatmand AR, Tadjerpisheh S, Brockmöller J, Tzvetkov MV. The prototypic pharmacogenetic drug debrisoquine is a substrate of the genetically polymorphic organic cation transporter OCT1. Biochem Pharmacol. 2012;83(10):1427–34.
22. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999;290(3):1482–92.
23. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, et al. Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997;16(7):10.
24. Wu X, Kekuda R, Huang W, Fei Y-J, Leibach FH, Chen J, et al. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998;273(49):32776–86.
25. Gründemann D, Harlfinger S, Golz S, Geerts A, Lazar A, Berkels R, et al. Discovery of the ergothioneine transporter. Proc Natl Acad Sci U S A. 2005;102(14):5256–61.
26. Nies AT, Koepsell H, Winter S, Burk O, Klein K, Kerb R, et al. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology. 2009;50(4):1227–40.
27. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76–85.
28. Weksler B, Romero I, Couraud P-O. The hCMEC/D3 cell line as a model of the human blood brain barrier. Fluids Barriers CNS. 2013;10(1):16.
29. Weksler BB, Subileau EA, Perrière N, Charneau P, Holloway K, Leveque M, et al. Blood–brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 2005;19(13):1872–4.
30. Kudris I, Skakun N, Orlova I, Libina V, Kulikov A. Analysis of amisulpride in human plasma by SPE and LC with fluorescence detection. Chromatographia. 2011;73(1–2):67–74.
31. Fisher DS, Partridge SJ, Handley SA, Couchman L, Morgan PE, Flanagan RJ. LC–MS/MS of some atypical antipsychotics in human plasma, serum, oral fluid and haemolysed whole blood. Forensic Sci Int. 2013;229(1–3):145–50.
32. Moon Y, Paek B, Kim H-H, Ji H, Lee H, Park H-G, et al. Determination of tiapride in human plasma using hydrophilic interaction liquid chromatography-tandem mass spectrometry. Arch Pharm Res. 2004;27(9):901–5.
33. Shnitsar V, Eckardt R, Gupta S, Grottker J, Müller GA, Koepsell H, et al. Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009;69(4):1494–501.
34. Stocker SL, Emami Riedmaier A, Schwab M, Giacomini KM. OCT (SLC22A) and OCTN family. Pharmacogenomics of Human Drug Transporters: John Wiley & Sons, Inc.; 2013. p. 171–208.
35. Geier EG, Chen EC, Webb A, Papp AC, Yee SW, Sadee W, et al. Profiling solute carrier transporters in the human blood–brain barrier. Clin Pharmacol Ther. 2013;94(6):636–9.
36. Pani L, Gessa GL. The substituted benzamides and their clinical potential on dysthymia and on the negative symptoms of schizophrenia. Mol Psychiatry. 2002;7(3):247–53.
37. Rama Rao VA, Bailey J, Bishop M, Coppen A. A clinical and pharmacodynamic evaluation of sulpiride. Psychopharmacology. 1981;73(1):77–80.
38. Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Silveira da Mota Neto Joaquim I, et al. Amisulpride versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews [Internet]. 2010; (1). Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006624.pub2/abstract.
39. Watanabe K, Sawano T, Endo T, Sakata M, Sato J. Studies on intestinal absorption of sulpiride (2): transepithelial transport of sulpiride across the human intestinal cell line caco-2. Biol Pharm Bull. 2002;25(10):1345–50.
40. Uchida Y, Ohtsuki S, Katsukura Y, Ikeda C, Suzuki T, Kamiie J, et al. Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors. J Neurochem. 2011;117(2):333–45.
41. Pauli-Magnus C, von Richter O, Burk O, Ziegler A, Mettang T, Eichelbaum M, et al. Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein. J Pharmacol Exp Ther. 2000;293(2):376–82.
42. Schmitt U, Abou El-Ela A, Guo LJ, Glavinas H, Krajcsi P, Baron JM, et al. Cyclosporine A (CsA) affects the pharmacodynamics and pharmacokinetics of the atypical antipsychotic amisulpride probably via inhibition of P-glycoprotein (P-gp). J Neural Transm. 2006;113(7):787–801.
43. Dauchy S, Miller F, Couraud P-O, Weaver RJ, Weksler B, Romero I-A, et al. Expression and transcriptional regulation of ABC transporters and cytochromes P450 in hCMEC/D3 human cerebral microvascular endothelial cells. Biochem Pharmacol. 2009;77(5):897–909.
44. Poller B, Gutmann H, Krähenbühl S, Weksler B, Romero I, Couraud P-O, et al. The human brain endothelial cell line hCMEC/D3 as a human blood–brain barrier model for drug transport studies. J Neurochem. 2008;107(5):1358–68.
45. Ohtsuki S, Ikeda C, Uchida Y, Sakamoto Y, Miller F, Glacial F, et al. Quantitative targeted absolute proteomic analysis of transporters, receptors and junction proteins for validation of human cerebral microvascular endothelial cell line hCMEC/D3 as a human blood–brain barrier model. Mol Pharm. 2012;10(1):289–96.
46. Feng B, Mills JB, Davidson RE, Mireles RJ, Janiszewski JS, Troutman MD, et al. In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the nervous system. Drug Metab Dispos. 2008;36(2):268–75.
47. Miecz D, Januszewicz E, Czeredys M, Hinton BT, Berezowski V, Cecchelli R, et al. Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood–brain barrier. J Neurochem. 2008;104(1):113–23.
48. Wiesel FA, Alfredsson G, Ehrnebo M, Sedvall G. The pharmacokinetics of intravenous and oral sulpiride in healthy human subjects. Eur J Clin Pharmacol. 1980;17(5):385–91.
49. Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G. A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol Clin Exp. 2002;17(1):1–13.
50. Han T, Everett RS, Proctor WR, Ng CM, Costales CL, Brouwer KLR, et al. Organic cation transporter 1 (OCT1/mOct1) is localized in the apical membrane of caco-2 cell monolayers and enterocytes. Mol Pharmacol. 2013;84(2):182–9.
51. Swift B, Nebot N, Lee JK, Han T, Proctor WR, Thakker DR, et al. Sorafenib Hepatobiliary disposition: mechanisms of hepatic uptake and disposition of generated metabolites. Drug Metab Dispos. 2013;41(6):1179–86.
52. Jung N, Lehmann C, Rubbert A, Knispel M, Hartmann P, van Lunzen J, et al. Relevance of the organic cation transporters 1 and 2 for antiretroviral drug therapy in human immunodeficiency virus infection. Drug Metab Dispos. 2008;36(8):1616–23.
53. Bennett K, Liu J, Hoelting C, Stoll J. Expression and analysis of two novel rat organic cation transporter homologs, SLC22A17 and SLC22A23. Mol Cell Biochem. 2011;352(1–2):143–54.
54. Okura T, Kato S, Takano Y, Sato T, Yamashita A, Morimoto R, et al. Functional characterization of rat plasma membrane monoamine transporter in the blood–brain and blood–cerebrospinal fluid barriers. J Pharm Sci. 2011;100(9):3924–38.