کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5814007 | 1556621 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The antiepileptic drug lamotrigine is a substrate of mouse and human breast cancer resistance protein (ABCG2)
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کلمات کلیدی
AEDCETAKO143TariquidarMDCKMitoxantronePharmacoresistanceTEERPGPMRPPhIP2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine - 2-amino-1-methyl-6-phenylimidazo [4،5-b] pyridineAUC - AUCP-glycoprotein - P-گلیکوپروتئینEpilepsy - بیماری صرعTopiramate - توپیرامات antiepileptic drug - داروهای ضدصرعBlood–brain barrier - سد خونی مغزیBBB - سد خونی مغزیValproate - سدیم والپرووات Phenobarbital - فنوباربیتالPhenytoin - فنی توئینLamotrigine - لاموتریژینlevetiracetam - لوتیراستامtransepithelial electrical resistance - مقاومت الکتریکی transepithelialarea under curve - منطقه تحت منحنیmultidrug resistance protein - پروتئین مقاوم در برابر چندین رژیمbreast cancer resistance protein - پروتئین مقاومت به سرطان سینهcarbamazepine - کاربامازپینMadin-Darby canine kidney - کلیه های سگ کوچولو Madin-Darby
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The antiepileptic drug lamotrigine is a substrate of mouse and human breast cancer resistance protein (ABCG2) The antiepileptic drug lamotrigine is a substrate of mouse and human breast cancer resistance protein (ABCG2)](/preview/png/5814007.png)
چکیده انگلیسی
Resistance to antiepileptic drugs (AEDs) is the major problem in the treatment of epilepsy. One hypothesis to explain AED resistance suggests that seizure-induced overexpression of efflux transporters at the blood-brain barrier (BBB) restricts AEDs to reach their brain targets. Various studies examined whether AEDs are substrates of P-glycoprotein (Pgp; MDR1; ABCB1), whereas information about the potential role of breast cancer resistance protein (BCRP; ABCG2) is scanty. We used a highly sensitive in vitro assay (concentration equilibrium transport assay; CETA) with MDCKII cells transduced with murine Bcrp1 or human BCRP to evaluate whether AEDs are substrates of this major efflux transporter. Six of 7 AEDs examined, namely phenytoin, phenobarbital, carbamazepine, levetiracetam, topiramate, and valproate, were not transported by Bcrp at therapeutic concentrations, whereas lamotrigine exhibited a marked asymmetric, Bcrp-mediated transport in the CETA, which could be almost completely inhibited with the Bcrp inhibitor Ko143. Significant but less marked transport of lamotrigine was determined in MDCK cells transfected with human BCRP. Lamotrigine is also a substrate of human Pgp, so that this drug is the first AED that has been identified as a dual substrate of the two major human efflux transporters at the BBB. Previous in vivo studies have demonstrated a synergistic or cooperative role of Pgp and Bcrp in the efflux of dual substrates at the BBB, so that transport of lamotrigine by Pgp and BCRP may be an important mechanism of pharmacoresistance in epilepsy patients in whom both transporters are overexpressed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 93, June 2015, Pages 7-14
Journal: Neuropharmacology - Volume 93, June 2015, Pages 7-14
نویسندگان
Kerstin Römermann, Renate Helmer, Wolfgang Löscher,