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CAS No. : 210245-80-0
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|Name:||Zonampanel; YM 872|
|Cat. No. :||CS-6830|
|CAS No. :||210245-80-0|
|M. Wt. :||331.24|
|Solubility:||10 mM in DMSO|
YM 872 is a selective antagonist of the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. In Vitro: YM 872 inhibits the human MRP4-mediated transport of [3H]oestradiol 17-D-glucuronide in a concentration-dependent manner. In contrast, YM 872 (up to 1000 mM) does not inhibit the human MRP2- or BCRP-mediated transport of [3H]oestradiol 17-D-glucuronide or [3H]methotrexate. YM 872 inhibits the uptake of typical substrates by Oat1, Oat2, and Oat3 with inhibition constant (Ki) values of 7.02 to 10.4 μM. A time- and saturable concentration-dependent increase in [14C]YM 872 uptake is observed in these cells [Km values: 13.4 to 53.6 μM]. In Vivo: In in vivo experiments, probenecid and cimetidine decrease intrinsic clearance for both the renal secretion and biliary excretion of YM 872.
Protocol:Animal Administration: Seven-week-old male Sprague-Dawley rats are used at 8 weeks after acclimatization for at least 1 week. During acclimatization, the rats are kept in an air-conditioned room with temperature and humidity controlled at 22.9 to 23.3°C and 50 to 78%; the room is lit for 12 h 30 min from 7:30 AM to 8:00 PM. Rats are given free access to solid food and water until just before drug administration. YM 872 (15 mg/kg) is administered at a single bolus dose into the rat tail vein with or without probenecid (50 mg/kg) or cimetidine (40 mg/kg). At 5, 15, and 30 min and 1, 2, 3, 4, and 6 h after dosing, blood is sampled under ether anesthesia via the inferior vena cava using a heparinized syringe and immediately stored on ice using four rats each per sampling time point per administration group (total of 128 rats for 8 sampling time points and 4 administration groups). Plasma is obtained by centrifugation at 4°C, 1870 g for 15 min and kept frozen at -20°C. Rats for plasma sampling at 3 and 6 h after administration are housed in metabolic cages after administration, spontaneously excreted urine is collected, and the cages are washed using water. Regarding specific gravity as 1, urine volume (including the cage-wash water) is calculated according to differences in the weight of the sampling tube before and after sampling. Urine samples are kept frozen at -20°C until assay as described below. All plasma and urine samples are protected from light throughout the sampling, storage, and assay procedures.
Minematsu T, et al. Role of organic anion transporters in the pharmacokinetics of zonampanel, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist, in rats. Drug Metab Dispos. 2008 Aug;36(8):1496-504.
Minematsu T, et al. Characterization of renal tubular apical efflux of zonampanel, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist, in humans. Xenobiotica. 2008 Sep;38(9):1191-202.
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