Add time:08/22/2019         Source:sciencedirect.com

SummaryAim of this study was to determine whether the carbon-11-labeled antiepileptic drug [11C]MEPHOBARBITAL (cas 115-38-8) is a substrate of P-glycoprotein (Pgp) and can be used to assess Pgp function at the blood–brain barrier (BBB) with positron emission tomography (PET). We performed paired PET scans in rats, wild-type (FVB) and Mdr1a/b(−/−) mice, before and after intravenous administration of the Pgp inhibitor tariquidar (15 mg/kg). Brain-to-blood AUC0–60 ratios in rats and brain AUC0–60 values of [11C]mephobarbital in wild-type and Mdr1a/b(−/−) mice were similar in scans 1 and 2, respectively, suggesting that in vivo brain distribution of [11C]mephobarbital is not influenced by Pgp efflux. Absence of Pgp transport was confirmed in vitro by performing concentration equilibrium transport assay in cell lines transfected with MDR1 or Mdr1a. PET experiments in wild-type mice, with and without pretreatment with the multidrug resistance protein (MRP) inhibitor MK571 (20 mg/kg), and in Mrp1(−/−) mice suggested that [11C]mephobarbital is also not transported by MRPs at the murine BBB, which was also supported by in vitro transport experiments using human MRP1-transfected cells. Our results are surprising, as phenobarbital, the N-desmethyl derivative of mephobarbital, has been shown to be a substrate of Pgp, which suggests that N-methylation abolishes Pgp affinity of barbiturates.

We also recommend Trading Suppliers and Manufacturers of MEPHOBARBITAL (cas 115-38-8). Pls Click Website Link as below: cas 115-38-8 suppliers