Dissertations / Theses on the topic 'OCTN2'
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Kwok, Bruce Chia-Wah. "Characterization on OCTN1 and OCTN2 in the human mammary gland." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ63172.pdf.
Full textOtt, Klaus. "Untersuchung von Polymorphismen mit möglicher funktioneller Relevanz in den Genen der organischen Kationentransporter OCTN1 und OCTN2 bei chronisch-entzündlichen Darmerkrankungen." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-97970.
Full textBonitz, Karina [Verfasser]. "Bedeutung des Carnitin-Transporters OCTN2 für die Entwicklung einer Herzinsuffizienz und eines akuten Myokardinfarktes. / Karina Bonitz." Greifswald : Universitätsbibliothek Greifswald, 2016. http://d-nb.info/1082001880/34.
Full textGrigat, Silke. "Analyse der Substratspezifität des Carnitin-Transporters SLC22A5 (OCTN2) von Mensch, Ratte und Huhn mittels LC-MS/MS /." Köln, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000253974.
Full textPagels, Stefanie [Verfasser], Peter [Akademischer Betreuer] Meisel, Gabriele [Akademischer Betreuer] Jedlitschky, Peter [Gutachter] Meisel, and Thomas [Gutachter] Hoffmann. "Untersuchungen zur Assoziation zwischen genetischen Varianten von OCTN1 und OCTN2 und Parodontitis: Ergebnisse aus der Bevölkerungsstudie Study of Health in Pomerania (SHIP-0) / Stefanie Pagels ; Gutachter: Peter Meisel, Thomas Hoffmann ; Peter Meisel, Gabriele Jedlitschky." Greifswald : Universität Greifswald, 2019. http://d-nb.info/1200547764/34.
Full textRödin, Mattias. "Characterization of the Carnitine Transporter, OCTN2: Functional Impact of Mutations and Its Role in COVID-19 Treatment Related Drug-Drug Interactions." Thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-416447.
Full textYamamoto, Priscila Akemi. "Impacto dos polimorfismos genéticos de OCT2 e OCTN1 na disposição cinética da gabapentina em pacientes com dor crônica /." Araraquara, 2018. http://hdl.handle.net/11449/154376.
Full textBanca: Rosângela Gonçalves Peccinini
Banca: Fabíola Dach
Resumo: A gabapentina (GAB) é um anticonvulsivante indicado para o tratamento de epilepsia e dor crônica. Possui cinética não linear relacionada a saturação do processo de absorção, não é metabolizada e é eliminada principalmente por excreção renal. Estudos sugerem a atividade dos transportadores de cátions orgânicos (OCT2 e OCTN1) na secreção renal da GAB. O objetivo do estudo foi investigar a influência dos polimorfismos genéticos de OCT2 e OCTN1 e outras possíveis covariáveis na disposição cinética da GAB em pacientes tratados com doses múltiplas. Os métodos de cromatografia líquida de alta eficiência com detecção por ultravioleta (CLAE-UV) para determinação da concentração de GAB no plasma e na urina foram desenvolvidos e validados segundo a RDC nº 27/2012 da ANVISA. Foi utilizado como agente derivatizante o 1-flúor-2,4-dinitrobenzeno, e como padrão interno o anlodipino. Os métodos apresentaram linearidade na faixa de 200-14.000 ng/mL de plasma e 2-120 µg/mL de urina. Foram investigados 66 participantes (35 mulheres e 31 homens), com idade média de 54 anos e com dor crônica tratados com GAB por pelo menos 7 dias. Os participantes foram genotipados como GG (n=58) e GT (n=8) para o polimorfismo SLC22A2 c.808G>T e CC (n=31), CT (n= 27) e TT (n=8) para o polimorfismo SLC22A4 c.1507C>T. As concentrações plasmáticas mínima de GAB no estado de equilíbrio variaram de 402,0 a 11.937,9 ng/mL durante tratamento com doses diárias que variaram de 600 a 3.600 mg. A idade e a taxa de filtração ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Gabapentin (GAB) is an anticonvulsant indicated for the treatment of epilepsy and chronic pain. It has nonlinear kinetics due to the saturation of absorption process, is not metabolized and is mainly eliminated by renal excretion. Studies suggest the activity of organic cation transporters (OCT2 and OCTN1) in the renal excretion of GAB. The aim of this study is to investigate the influence of genetic polymorphisms of OCT2 and OCTN1 and other possible covariates on the kinetic disposition of GAB in patients treated with multiple doses. High performance liquid chromatography with ultraviolet detection (HPLC-UV) methods for the determination of GAB plasma and urine concentration were developed and validated according to RDC nº 27/2012 of ANVISA. 1-fluoro-2,4-dinitrobenzene was used as derivatization agent, and amlodipine as internal standard. The methods showed linearity in the range of 20014,000 ng/mL of plasma and 2-120 µg/mL of urine. Sixty-six participants (35 women and 31 men), with mean age of 54 years and with chronic pain treated with GAB for at least 7 days were investigated. They were genotyped as GG (n=58) and GT (n=8) for SLC22A2 c.808G>T polymorphism and as CC (n=31), CT (n=27) and TT (n=8) for SLC22A4 c.1507C>T polymorphism. GAB steady-state minimum plasma concentrations ranged from 402.0 to 11,937.9 ng/mL during the treatment with daily doses ranging from 600 to 3,600 mg. Age and estimated glomerular filtrate rate showed significant correlation with the plasma concentration of GAB/daily dose ratio. Other variables (gender, body weight and body mass index) were not correlated. The estimated glomerular filtration rate and daily dose were found as significant covariates to predict GAB minimum plasma concentration at steady-state, explained 68% of plasma concentration variability. The population pharmacokinetics showed... (Complete abstract click electronic access below)
Mestre
Friedrich, Anne. "Studies of the expression and characterization of various transport systems at RBE4 cells, an in vitro model of the blood-brain barrier." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2003. http://nbn-resolving.de/urn:nbn:de:swb:14-1060258657421-84155.
Full textFriedrich, Anne. "Studies of the expression and characterization of various transport systems at RBE4 cells, an in vitro model of the blood-brain barrier." Doctoral thesis, Technische Universität Dresden, 2002. https://tud.qucosa.de/id/qucosa%3A23820.
Full textFink, Matthias Alexander [Verfasser], Henry W. S. [Akademischer Betreuer] Schroeder, Sandra [Akademischer Betreuer] Bien-Möller, Henry W. S. [Gutachter] Schroeder, and Veit [Gutachter] Rohde. "Untersuchungen zur prognostischen Relevanz des L-Carnitin-Transporters OCTN2 im Glioblastoma multiforme mit in vitro-Charakterisierung seines zytoprotektiv wirksamen Substrats L-Carnitin in humanen Glioblastomzellen / Matthias Alexander Fink ; Gutachter: Henry W. S. Schroeder, Veit Rohde ; Henry W. S. Schroeder, Sandra Bien-Möller." Greifswald : Universität Greifswald, 2019. http://d-nb.info/119416272X/34.
Full textFink, Matthias Alexander [Verfasser], Henry [Akademischer Betreuer] Schroeder, Sandra [Akademischer Betreuer] Bien-Möller, Henry W. S. [Gutachter] Schroeder, and Veit [Gutachter] Rohde. "Untersuchungen zur prognostischen Relevanz des L-Carnitin-Transporters OCTN2 im Glioblastoma multiforme mit in vitro-Charakterisierung seines zytoprotektiv wirksamen Substrats L-Carnitin in humanen Glioblastomzellen / Matthias Alexander Fink ; Gutachter: Henry W. S. Schroeder, Veit Rohde ; Henry W. S. Schroeder, Sandra Bien-Möller." Greifswald : Universität Greifswald, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:9-opus-29273.
Full textJohansson, Karin. "Analysis of immunoglobulin gene expression focus on Oct2 /." Lund : Dept. of Cell and Molecular Biology, Lund University, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39776663.html.
Full textAnderson, Jason T. PharmD. "Role of OCTN1 (SLC22A4) in the Disposition of Nucleoside Analogs in AML." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1573744863552166.
Full textFilipski, Kelly K. "Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity." View the abstract Download the full-text PDF version, 2009. http://etd.utmem.edu/ABSTRACTS/2009-022-Filipski-index.htm.
Full textTitle from title page screen (viewed on August 6, 2009). Research advisor: Alex Sparreboom, Ph.D. Document formatted into pages (ix, 79 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 74-78).
Cortez, Pacheco Renzo Manuel. "Caracterización del exón 4 del gen SLC22A2 (OCT2) en poblaciones peruanas." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2020. https://hdl.handle.net/20.500.12672/11555.
Full textTesis
Harper, Jaclyn Nicole. "Multiple Mechanisms of Ligand Interaction with the Human Organic Cation Transporter, OCT2." Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/297644.
Full textAkinci, Sibel. "Die Rolle der organischen Kationentransporter OCT1, OCT2 und OCT3 bei der Serotonin-induzierten Bronchokonstriktion der Maus." Giessen : VVB Laufersweiler, 2006. http://geb.uni-giessen.de/geb/volltexte/2007/4336/index.html.
Full textAkinci, Sibel [Verfasser]. "Die Rolle der organischen Kationentransporter OCT1, OCT2 und OCT3 bei der Serotonin-induzierten Bronchokonstriktion der Maus / eingereicht von Sibel Akinci." Giessen : VVB Laufersweiler, 2007. http://d-nb.info/988664453/34.
Full textPraeger, Damaris. "Variabilität der Expression des Carnitin-Transporters OCTN2 im humanen Herzen /." 2006. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=017107386&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
Full textOtt, Klaus [Verfasser]. "Untersuchung von Polymorphismen mit möglicher funktioneller Relevanz in den Genen der organischen Kationentransporter OCTN1 und OCTN2 bei chronisch-entzündlichen Darmerkrankungen / vorgelegt von Klaus Ott." 2009. http://d-nb.info/993555276/34.
Full textWu, Chiung-Chuan, and 吳瓊娟. "Neonatal screening of a mutation (R254X) of SLC22A5 (OCTN2) in Primary Carnitine Deficiency." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/51769581833685920921.
Full text國立臺灣大學
分子醫學研究所
97
Mutations in the SLC22A5 gene, which encodes the plasma membrane carnitine transporter OCTN2, cause primary carnitine deficiency (PCD). Currently, PCD is screened in newborns using free carnitine level as a marker. However, owing to the high free carnitine level in the maternal circulation, the affected babies may not have a free carnitine level low enough to be picked up by screening. Previously, the OCTN2 gene c.981 C>T (p.R254X) mutation was found to be common in the Southern Chinese population. Therefore, in this study we want to see if molecular diagnosis could enhance newborn screening of PCD. In this study, we analyzed blood spot DNA OCTN2 gene p.R254X mutation. We first analyzed 348 random anonymous control DNA samples to see the prevance of this mutation in the population. We then analyzed 48 blood spot samples in which free carnitine level was lower than 11µM (the standard cut off for free carnitine was lower than 6.44 μΜ). We found that among the three methods for blood spot DNA extreaction (the methanol method, boiling method, and QIAamp method); the QIAmp method gave the best result. We then found two p.R254X heterozygotes in the 348 control DNA (1in 174); another two p.R254X heterozygotes in the 48 samples with low free carnitine level (1 in 24). In comparison to previous data, newborns with low free carnitine level did have a higher prevalence of OCTN2 gene p.R254X mutation (p=0.01996). Babies who had both low free carnitine and OCTN2 mutation should have a higher chance to be a patient of primary carnitine deficiency, and their disease status should be determined. This method, therefore, increases the sensitivity of detecton of PCD without increase the false positive rate of the screening.
"Inflammation affects ontogeny of L-carnitine hmeostasis mechanisms in the developing rat." Thesis, 2013. http://hdl.handle.net/10388/ETD-2013-12-1373.
Full textHsu, Chen-Chi, and 徐晨綺. "Mechanistic study of thiazolidinediones-mediated regulation of novel organic cation transporter type II (OCTN2) in BeWo cells." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/78820873925051546341.
Full text國立臺灣大學
藥學研究所
99
Carnitine is important for the transfer of acry-carnitine with long-chain fatty acids, which is then transported into mitochondria for β-oxidation. The fetus cannot synthesize adequate amount of carnitine, and the active transfer of carnitine from the mother to the fetus is important. The novel organic cation transporter 2 (OCTN2) is a high-affinity carnitine transporter. In current study, we investigate the effects of thiazolidinediones on placental OCTN2 expression and the underlying mechanisms in human choriocarcinoma BeWo cells. In addition, OCTN2 expression was measured in human placentas isolated from pregnancy with or without preeclampsia. After treatment of troglitazone, rosiglitazone and pioglitazone in BeWo cells, the mRNA and protein levels were analyzed by RT-qPCR and Western blotting, respectively. The results showed that, after 72 hr of treatment with troglitazone (10 μM), OCTN2 mRNA expression was significantly reduced by 60% in BeWo cells. In contrast, rosiglitazone (10 μM) and pioglitazone (10 μM) did not cause any change in OCTN2 mRNA expression in BeWo cells. Results of OCTN2 protein expression were consistent with those in mRNA. Troglitazone treatment significantly reduced both PPARα and RXRα mRNA levels. In contrast, treatment with rosiglitazone or pioglitazone did not reduce PPARα or RXRα mRNA expression. Both mRNA and protein levels of HIF-1α were increased by troglitazone treatment in BeWo cells, along with an increase in p38 activity and a decrease in Erk activity. In addition, the expression of OCTN2 and PPARα protein was significantly reduced in human placenta explants by hypoxia treatment and in placentas isolated from preeclampsia. In conclusion, troglitazone, but not rosiglitazone or pioglitazone, regulates OCTN2 and HIF-1α expression in placental choriocarcinoma BeWo cells and this effect may be mediated by mitogen-activated protein kinase. Hypoxia treatment caused a decrease in OCTN2 and PPARα expression in human placenta explants, which resembles the findings in preeclamptic placentas.
Tseng, Yi-Chi, and 曾奕淇. "EFFECT OF FORSKOLIN ON THE EXPRESSION ANDFUNCTION OF ORGANIC CATION TRANSPORTERNOVEL TYPE II (OCTN2) IN HUMAN CHORIOCARCINOMABeWo CELLS." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/15621608576028482387.
Full text國立臺灣大學
藥學研究所
94
L-carnitine is important for beta-oxidation of fatty acids and intracellular coenzyme A homeostasis. Given that the carnitine biosynthesis is immature in fetal organisms, it is pivotal for fetal organism to acquire carnitine to maintain normal functions. It is known that carnitine is mainly transported across placenta via organic cation transporter novel type II (OCTN2), a high affinity and sodium dependent carnitine transporter. BeWo cell is derived from human choriocarcinoma and can be induced to differentiate into syncytiotrophoblast by forskolin and has therefore been used as an in vitro placenta model. In the current study, BeWo treated with forskolin was used as a model for syncytiotrophoblast. Results from RT-PCR analysis showed that the expression level of OCTN2 was downregulated after 100 uM forskolin treatment. Uptake of 3H-labeled L-carnitine was sodium dependent and saturable (Km = 27.1 ± 11.8 uM, Vmax = 702 ± 132 pmol/30 min/mg protein) with a non-saturable constant k equals to 6.02 ± 1.21 (uL/30 min/mg protein). The values of kinetic parameters changed after forskolin treatment (Km = 72.6 ± 5.4 uM, Vmax = 1805 ± 420 pmol/30 min/mg protein, k = 2.25 ± 0.59 uL/30 min/mg protein). These results suggest that the expression level and function of OCTN2 are both changed during syncytialisation. IC50 for several drugs of carnitine uptake were also determinated to understand the effect on drug-OCTN2 interaction during syncytialisation induced by forskolin.
Chang, Ting-Ting, and 張婷婷. "Effect of hypoxia on the expression of organic cation transporter novel type II (OCTN2) in human choriocarcinoma BeWo cells." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/65211488860935083763.
Full text國立臺灣大學
藥學研究所
97
The syncytiotrophoblast of human placenta is an important interface mediating substance transfer between the mother and the fetus. Preeclampsia, a serious complication during pregnancy, is associated with impaired syncytialization. Carnitine is responsible for the transport of long-chain fatty acids into mitochondria, which is then undergoing β-oxidation for cellular energy production. However, the fetus cannot synthesize adequate amount of carnitine, and the active transfer of carnitine from the mother to the fetus is important. The novel organic cation transporter 2 (OCTN2) is a high-affinity carnitine transporter in human placenta. It was reported that plasma carnitine concentrations in pregnant women with preeclampsia increased about 50 % compared with healthy pregnant women. Hence, the aim of this study was to investigate the effects of hypoxic condition on the regulation of OCTN2 in human choriocarcinoma BeWo cells. BeWo cells were cultured under 0.5 % O2 for mimicking hypoxic condition. The protein expression of syncytin, OCTN2, and PDZK1 in crude membrane of BeWo cells was analyzed by Western blot analysis, and the nuclear expression of HIF-1α, HIF-2α, PPARα and RXRα was also measured to explore possible mechanisms in regulating OCTN2 under hypoxic condition. Under forskolin-induced syncytialization, syncytin and OCTN2 were increased, whereas both of them were decreased in hypoxic condition. PDZK1 was significantly downregulated after syncytialization, whereas it was slightly increased under hypoxia. HIF-1α and HIF-2α were upregulated at 4 hours and then decreased at 24 hours after hypoxia treatment. Both of PPARα and RXRα were significantly downregulated at 24 hours. However, OCTN2 expression was increased upon treatment PPARα agonist, WY14643. The activation of OCTN2 expression was also upregulated by WY14643 under hypoxic condition. Afterward, cellular uptake of 3H-labeled L-carnitine was measured after hypoxia and WY14643 treatment. The results showed that the values of carnitine uptake was increased upon WY14643 treatment, however it was decreased under hypoxia condition. We also observed human normal and preeclamptic placental tissue by immunohistochemistry. Both of OCTN2 and PPARα protein expression were decreased in human preeclamptic placentas. In conclusion, the process of syncytialization, OCTN2 protein expression and carnitine uptake was inhibited under hypoxic condition. According to the results of immunohistochemistry, we speculate the plasma carnitine concentrations accumulation in preeclamptic pregnant women can be due to the downregulated OCTN2 expression. Furthermore, we also provide evidences that PPARα is one of the important factors that regulate the expression of OCTN2. If there are any other factors involved in regulating OCTN2 should be verified.
Huang, Fu-De, and 黃富德. "Investigation of mechanisms regulating protein expression and function of organic cation transporter novel type II (OCTN2) during syncytialization in human choriocarcinoma BeWo cells." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/97202743496352023281.
Full text國立臺灣大學
藥學研究所
96
The syncytiotrophoblast of human placenta provides an essential surface in mediating the transfer of drugs and nutrients between the mother and the fetus. Syncytialization is an important process for the development of functional placenta. Carnitine is important for the transport of long-chain fatty acid to mitochondria, which is then subjected to β-oxidation. However, the carnitine biosynthesis in fetal organisms is immature and placental transfer of carnitine from maternal blood is required. Given the essential role of carnitine for fetal development, the purpose of the current study was to investigate the effects of syncytialization on the expression and function of OCTN2, a high-affinity carnitine transporter. The forskolin induced syncytialization of BeWo cells was used as an in vitro model for placental trophoblast in this study. Crude membrane fraction and brush border membrane were isolated. The mRNA and protein expression of syncytin were analyzed to test whether forskolin treatment can induce syncytialization in BeWo cells. The change in the expression of OCTN2 and adapter proteins, PDZK1, PDZK2, NHERF1 and NHERF2, under forskolin treatment was analyzed by Western blot. Afterward, cellular uptake of 3H-labeled L-carnitine was measured and kinetic analysis was performed. The results showed that forskolin can increase the mRNA and protein expression of syncytin. Protein expression of OCTN2 is increased under long-term forskolin treatment. However, the kinetic study showed that the Vm values of carnitine uptake remained unchanged and the Km values increased. Both PDZK1 and NHERF1 protein expression were decreased after forskolin treatment. In conclusion, protein and function of OCTN2 can be regulated during syncytialization. OCTN2 protein is up-regulated, whereas PDZK1, the functional regulator of OCTN2, is decreased and result in the unchanged Vmax. The regulation of PDZK1 on other transporters during syncytialization should be further varified.
Müller, Judith. "Expression von Aufnahme-Transportern für Zytostatika in Mamma- und Prostatakarzinom-Zellen und ihre Interaktion mit Zytostatika." Doctoral thesis, 2017. http://hdl.handle.net/11858/00-1735-0000-0023-3E8D-4.
Full textNovotná, Kateřina. "Interakce gilteritinibu s transportéry OCT1 a OCT2; vztah ke konvenční terapii akutní myeloidní leukémie." Master's thesis, 2021. http://www.nusl.cz/ntk/nusl-446641.
Full textWilson, Nina Claire. "Identification of single nucleotide polymorphisms within the OCT2 gene in the South African black population." Thesis, 2016. http://hdl.handle.net/10539/21741.
Full textThe Organic Cation Transporter 2 (OCT2) gene is responsible for facilitating the transport of cationic compounds, which include both endogenous substrates and clinical drugs. Single nucleotide polymorphisms (SNPs) within this gene were extensively explored in the South African black population as little research has been conducted on these individuals so far. We sequenced the OCT2 promoter region of 10 DNA samples from the South African black population and identified four SNPs and one INDEL. We performed a luciferase assay to determine their effects on gene expression and we found two variants (rs59695691 and rs138765638) that showed a statistically significant change in luciferase expression suggesting that they may be associated with a change in OCT2 regulatory function. We also indentified thirteen SNPs and two INDELs within the OCT2 promoter region, and nine SNPs within the OCT2 coding region through analysing various South African population studies. These variations could affect both gene expression and protein function. These findings help contribute to filling the gap pertaining to OCT variation in South African populations.
LG2017
Harlfinger, Stephanie [Verfasser]. "Identifizierung des physiologischen Substrates und funktionelle Charakterisierung des organischen Kationentransporters OCTN1 mittels LC-MS/MS / vorgelegt von Stephanie Harlfinger." 2005. http://d-nb.info/977987957/34.
Full textEy, Janine [Verfasser]. "Der organische Kationentransporter OCTN1 und sein biogenes Substrat Ergothionein : Vorkommen in Nahrungsmitteln, antioxidative und proliferationsfördernde Eigenschaften / vorgelegt von Janine Ey." 2009. http://d-nb.info/996572775/34.
Full textTai, Ying, and 戴瑩. "Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP-induced dopaminergic toxicity." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/04727839317679770639.
Full text臺灣大學
藥學研究所
98
Exposure to the chemical 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) can lead to the presence of its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP+), in the brain, which induces a selective destruction of dopaminergic nigrostriatal neurons and the occurance of Parkinson’s disease. Amantadine is used in the treatment of Parkinson’s disease. However, its mechanism is not fully understood. Amantadine is known to be as substrate of organic cation transporters (OCTs). The purpose of this study was to evaluate the effects of amantadine on blood-brain barrier (BBB) transport of MPTP, and on MPTP-induced dopaminergic toxicity. Also, the expression and cellular localization of OCTs were investigated. The role of OCTs on MPTP uptake was studied in brain microvessel endothelial cells (BMECs). The results of in vivo brain microdialysis showed that amantadine significantly reduced the area under the time-concentration curves of MPTP and MPP+ in brain extracellular fluid in rats and mice. Likewise, amantadine increased the level of dopamine and dopamine metabolites in brain striatum of mice, compared with mice recieving MPTP only. PET scan showed amantadine ameliorated MPTP-induced dopaminergic toxicity in the brain of mice. The confocal and Western blot analyses showed that OCT1 and OCT2 were mainly expressed on the luminal side of BMECs and adult rat brain endothelial cells (ARBECs). Cellular uptake of MPTP was decreased with OCT1/OCT2 silencing in BMECs and ARBECs. In conclusion, amantadine reduces the BBB transfer of MPTP and MPTP-induced dopaminergic toxicity in rodents, and OCT1 and OCT2 are important for MPTP transfer across the BBB.