Background:

Zonampanel (YM 872) is a selective antagonist of the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor.

Zonampanel inhibits the human MRP4-mediated transport of [3H]oestradiol 17-D-glucuronide in a concentration-dependent manner. In contrast, Zonampanel (up to 1000 mM) does not inhibit the human MRP2- or BCRP-mediated transport of [3H]oestradiol 17-D-glucuronide or [3H]methotrexate[1]. Zonampanel 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]Zonampanel uptake is observed in these cells [Km values: 13.4 to 53.6 μM][2].

In in vivo experiments, probenecid and cimetidine decrease intrinsic clearance for both the renal secretion and biliary excretion of Zonampanel[2].

[1]. 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. [2]. 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.